W4122: Beneficial and Adverse Effects of Natural Chemicals on Human Health and Food Safety

(Multistate Research Project)

Status: Inactive/Terminating

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SAES-422 Reports

Annual/Termination Reports:

[01/05/2018] [12/04/2018] [12/08/2019] [01/26/2021] [12/12/2021]

Date of Annual Report: 01/05/2018

Report Information

Annual Meeting Dates: 10/05/2017 - 10/06/2017
Period the Report Covers: 10/01/2016 - 09/30/2017

Participants

Chen, Chi – University of Minnesota; Chicco, Adam – Colorado State University; Coulombe, Roger – Utah State University; Delgado, Efren – New Mexico State University; Harrington, Mike – Colorado State University; Helferich, William – University of Illinois; Majumder, Kaustav– University of Nebraska – Lincoln; Munson-McGee, Stuart – New Mexico State University; Nerurkar, Pratibha – University of Hawaii (through Skype); Pestka, James – Michigan State University; Turner, Nancy – Texas A&M University; Weir, Tiffany – Colorado State University; Williams, David – Oregon State University; Zhu, Meijun – Washington State University

Participants Attachment:

W-4122 report-20171127.docx

Brief Summary of Minutes

The 2017 Annual Meeting of the W-4122 Multistate Group was called to order by the Chair, Dr. Meijun Zhu in the morning of October 5^th. Dr. Mike Harrington (WAAESD) provided an overview of the status of the multi-state program, the current funding priorities identified in the NIFA strategic plan, and budget status at NIFA. Last year, this group was recognized with the Western Region Award of Excellence in Multistate Research. Dr. Harrington would like to resubmit a nomination for W4122 to be considered for the national award again this year. This year, we have five new members attend the meeting. Each member present delivered a presentation to update the group on his/her progress (content summarized in the Annual Group Report). At the business meeting, new officers for 2017-2018 were selected: Chair, Adam Chicco (CSU); Vice-Chair, Stuart Monson (NMSU); and Secretary, Chi Chen (UMn). Also, the dates for the 2017 annual meeting will be October 4-5 and the meeting will be held in Calistoga, CA.

Accomplishments

Objective 1: Examine the effects of phytochemicals and other dietary components on gut microbiota and intestinal function. MI Station studies environment and diet influence latency/severity of genome-driven autoimmune disease (AD). In female NZBWF1 mice, a model for the prototypical AD lupus, intranasal installation with crystalline silica (cSiO2) triggers premature loss of self-tolerance in the lung as evidenced by robust ectopic lymphoneogenesis thereby accelerating/ exacerbating systemic autoimmunity and glomerulonephritis. Remarkably, dietary supplementation with the ω-3 polyunsaturated fatty acid (PUFA), docosahexaenoic acid (DHA), abrogates cSiO2-accelerated autoimmunity. They assessed the time-dependent effects of DHA consumption on cSiO2-triggered pulmonary autoimmune gene expression. Cohorts (n=8/gp) of 6-wk old female NZBWF1 mice were fed an isocaloric AIN-93G diet containing 0.0, 0.4, or 1.0% DHA (equivalent to human DHA supplement consumption at 0, 2, and 5 g/d, respectively) for 2 wk. Mice were then intranasally instilled with 1.0 mg cSiO2 or vehicle once per week for 4 wk and then maintained on experimental diets for 1,5, 9, or 13 wk. Cohorts were sacrificed, total RNA isolated from lungs, and gene expression levels using an nCounter® PanCancer Immune Profiling module, a multiplexed method for 800 immune-related target genes. cSiO2 induced expression of 48, 90, 106, and 99 autoimmune-related genes by more than 1.5-fold (p>0.05) in the 1, 5, 9, and 13 wk cohorts, respectively. Upregulated genes included interferon-driven proteins, chemokines, cytokines, complement, and macrophage/lymphocyte activation markers. Diets containing low and high DHA concentrations blocked expression of 80-90 % and 100 %, respectively, of the autoimmune genes triggered by cSiO2. These results suggest that DHA supplementation at physiologically relevant doses might be useful in preventing cSiO2 triggering of lupus and other AD. HI Station demonstrated that Momordica charantia (bitter melon, BM) and Morinda citrifolia (noni) improves glucose and lipid metabolism as well as prevents weight gain in high-fat diet (HFD)-fed mice. These improved metabolic activity by BM and noni was in part due to improvement of intestinal health by ameliorating intestinal inflammation, preserving gut barrier integrity and maintaining a healthy gut microbiome. Similarly, the differential effects of commercial and laboratory-prepared noni juice on glucose metabolism were also associated with improving gut microbial dysbiosis in HFD-fed mice. OR Station focused on studying dietary chemoprevention of cancer. They are employing a mouse model of transplacental cancer to determine in dietary supplementation of the pregnant mouse can provide protection for the fetus/infant with respect to development of cancer as adults from the in utero exposure. The primary emphasis has been on phytochemicals from cruciferous vegetables primarily indole-3-carbinol (I3C) and sulforaphane (SFN). They are studying the role of Nrf-2 signaling in the chemoprevention due to SFN. In a recent development, they are utilizing zebrafish as a xenograft model for human cancer cells. By pretreating the zebrafish embryos with I3C prior to injection with human leukemia cells from pediatric patients they are assessing the potency and efficacy of I3C in prevention of these cells from proliferation and metastasis. TX Station demonstrated that polyphenol-rich sorghum brans influence the colon microbiota of healthy rats, or those induced to have colitis. The diets included sorghum brans that contain condensed tannins, or deoxyanthocyanins, or a combination of the two. The patterns found in rats consuming a diet without the sorghum brans were reflective of those found in obese individuals or those with inflammatory bowel disease. Importantly, it was possible to protect against this shift by including a single, polyphenol-rich fiber source, and to reduce the colon damage associated with induction of colitis. Beneficial changes in the colon microbiota of rats was observed when a dried plum puree was included in the diet. Alterations in the microbiota contributed to modifications in the fecal metabolome. WA Station examined roles of AMPK in intestinal epithelial differentiation using in vivo and in vitro system. Adenosine monophosphate-activated protein kinase (AMPK) is a master regulator of energy metabolism and recently recognized for its important regulatory role in cell differentiation. The microbial metabolite, butyrate, and polyphenolic compounds enhance barrier function, which were associated with the activation of AMPK. However, the role of AMPK in intestinal epithelial differentiation has not been studied directly. They found that AMPK activation improved the barrier function of Caco-2 cells as indicated by increased transepithelial electrical resistance and reduced paracellular FITC-dextran permeability, which was associated with enhanced epithelial differentiation. They further found that AMPK enhances intestinal barrier function and epithelial differentiation via promoting caudal type homeobox 2 (CDX2) expression, a critical transcription factor governing epithelial differentiation. CO Station examined whether gut dysbiosis is a causal factor in obesity-related arterial stiffness and endothelial dysfunction. To this end, they determined that obesity-associated vascular dysfubnction was accompanied by global shifts in the gut microbiota and specifically, that three species of Bifidobacterium that were reduced by western diet negatively correlated with multiple measures of vascular dysfunction. To determine whether western diet-induced alterations in the microbiota were causally related to the development of vascular dysfunction, dysbiosis in western diet-fed mice was abated by administration of a broad-spectrum antibiotic cocktail for 8 weeks despite no significant changes to body weight or body fat distribution. Given that bacterial lipopolysaccharide (LPS) has been implicated as a causal role in gut-derived systemic inflammation that leads to cardiometabolic aberrations, they examined LPS as a possible link between vascular function and gut dysbiosis. They observed that five months of western diet feeding caused a marked increase in circulating lipopolysaccharide-binding protein (LBP), a surrogate marker for LPS, and that it was significantly reduced following antibiotic treatment, suggesting that the vascular-protective effects of antibiotics involve reductions in LPS signaling. They also observed downstream inflammatory mediators regulated by LPS (IL-6 and phosphorylated NF-ĸB) were also higher in obese animals and reduced with antibiotics. Finally, to confirm that LPS is capable of inducing vascular dysfunction, and to examine the role of TLR4 in this process, they incubated arteries from control mice and from TLR4-/- mice with LPS for 60 minutes. Acute LPS incubation caused significant endothelial dysfunction in arteries from wild-type mice, but not TLR4-/- mice, confirming that LPS can mediate vascular dysfunction via TLR4 signaling. Objective 2: Identify cellular mechanisms and host molecular targets of beneficial or adverse dietary components that influence human health. UT Station is studying possible epigenetic mechanisms for the observed silencing of the GSTA3/A4 genes in domesticated turkey (DT), which potentially underlies the extreme sensitivity to dietary carcinogens lkike aflatoxin B1 (AFB1). By contrast, wild turkeys (WT) have GSTs capable of detoxifying AFB1, and are hence more resistant than DT. Changes in methylation, particularly at CpG sites clustered in the promoter region of a gene, can lead to changes in expression. To identify whether methylation differences may be responsible for GST silencing in domesticated turkeys, they searched for CpG islands "upstream" of the 5' end GSTA3 and GSTA4 genes. CpG sites in the GSTA region occur less frequently than expected by chance, with apparent CpG islands near the 5' ends of most of the GSTA genes, but not GSTA3--the one that are most interested in.They tested for differences between WT and DT livers in the methylation level of the CpG island upstream of GSTA4 and found that methylation levels in this region are low (~1.5%) with no significant difference between these two turkey types. There are only 88 CpGs spread over the 11000bp upstream of GSTA3, but half of those CpGs are concentrated in four 500bp sections within 2500bp of the transcription start site, so they searched for potential methylation differences in those four regions. Preliminary results suggest that methylation in these regions does not differ between WT and DT. Even though these four regions have a higher density of CpGs than the rest of the sequence upstream of GSTA3, it is still a much lower density than the CpG islands upstream of other genes, raising questions about whether these CpG sites are part of a promoter or whether the promoter for GSTA3 is located elsewhere in the genome, potentially shared with another gene. They also looked for differences in the presence or absence of CpG sites in the suspected promoter regions of GSTA3 and GSTA4 due to known SNPs between WT and DT. There are SNPs in these regions but they do not affect CpG sites. MI Station explored mechanisms of how the common food toxin deoxynivalenol (DON, vomitoxin) evokes anorexia and vomiting can shed new light on in what manner calcimimetics cause problematic side effects in the digestive tract. In prior work, their lab demonstrated that gut enteroendocrine cells (EECs) secrete hormones that mediate DON’s anorectic and emetic effects. Using STC-1 cells, a cloned EEC model, they discovered that DON-induced activation of CaSR and transient receptor ankyrin-1 channel (TRPA1) drives Ca2+-mediated hormone secretion. However, the roles of CaSR and TRPA1 in DON’s anorectic and emetic effects remain unclear. To understand the mechanism of anorexia, they tested the hypothesis that DON-induced food refusal and satiety hormone release in the mouse are linked to activation of CaSR and TRPA1. Oral treatment with selective agonists for CaSR (R-568) or TRPA1 (allyl isothiocyanate, AITC) suppressed food intake in mice and the agonists’ effects were blocked by pretreatment with corresponding antagonists NPS-2143 or ruthenium red (RR), respectively. NPS-2143 or RR inhibited both DON-induced food refusal as well as plasma elevations of the satiety hormones cholecystokinin (CCK) and peptide YY3-36 (PYY3-36) which are well known to mediate reduced appetite and impair food consumption. Co-treatment with both antagonists additively suppressed both anorectic and hormone responses to DON. To elucidate whether similar mechanisms were involved in vomiting, they further tested the hypothesis that DON triggers emesis in mink by activating CaSR and TRPA1. Oral gavage with selective agonists for CaSR (R-568) or TRPA1 (AITC) rapidly elicited emesis in the mink in dose-dependent fashion. Oral pretreatment the animals with their corresponding antagonists NPS-2143 or RR, respectively, inhibited these responses. DON-induced emesis in mink was similarly inhibited by oral pretreatment with NPS-2143 or RR. In addition, these antagonists suppressed concurrent DON-induced elevations in plasma peptide YY3-36 and 5-hydroxytryptamine – hormones previously demonstrated to mediate the toxin’s emetic effects in mink. Furthermore, antagonist co-treatment additively suppressed DON-induced emesis and peptide YY 3-36 release. The major findings of these animal studies along with prior findings by their laboratory support the contention that CaSR and TRPA1 activation contribute to DON-induced food refusal and emesis by mediating hormone exocytosis from EEC. Implicit in these findings, is the suggestion that calcimimetics induce digestive tract side effects in humans by promoting the release of enteroendocrine hormones. OR Station currently focuses on mechanisms of action and biomarkers associated with an important class (3 of the top 10 ATSDR environmental chemicals of concern), polycyclic aromatic hydrocarbons (PAHs), of food-borne carcinogens as well as the cooked meat mutagens (also known human carcinogens). They have accumulated evidence from the mouse transplacental model and adult rodent colon and prostate cancer models that PAHs and cooked meat mutagens are capable of altering the epigenome including microRNAs and long non-coding RNAs. Currently, they are collaborating with Lawrence Livermore National Laboratory to employ accelerator mass (AMS) spectrometry to determine the fate of orally absorbed benzo[a]pyrene (BaP), a PAH common in food and ranked as a known human carcinogen by the International Agency for Research on Cancer (IARC). IL Station investigated the effects of inadequate dietary calcium (Ca) on bone turnover, tumor growth, and bone response to tumor in tibia inoculated with 4T1 mammary carcinoma cells using Balb/c mice. Nine-month-old female Balb/c mice were placed on an adequate Ca (5 g/kg diet, n=30) or low Ca (80 mg/kg diet, n=31) diet for 14 days, then injected intratibially with 1,000 4T1 cells (transfected with luciferase for bioluminescence imaging), and sacrificed at 5, 10, or 21 days post-inoculation (n=7-10 mice/group). Control mice (n=6/group) were injected with carrier and sacrificed at 10 days post-inoculation. Tibiae with muscle intact were excised and evaluated by microcomputed tomography and histology. In vivo bioluminescent imaging revealed that 4T1 cells metastasized to lung. Therefore, lungs were further removed for quantification of tumor. Mice fed low Ca exhibited higher bone turnover and higher tibial lesion scores than mice fed adequate Ca. Lesion severity, manifested as cortical osteolysis and periosteal woven bone formation, and tumor cell infiltration to muscle, increased with time, irrespective of diet. However, for most skeletal endpoints the rates of increase were greater in mice consuming low Ca compared to mice consuming adequate Ca. Infiltration of tumor cells into adjacent muscle, but not metastasis to lung, was also greater in mice consuming low Ca diet. The findings suggest that high bone turnover due to Ca insufficiency results in greater local mammary tumor cell growth, cortical osteolysis, woven bone formation, and invasion to muscle in mice. TX Station found that radiation altered the proportion of stem cells in the colon crypts, and that a diet containing fish oil and pectin was able to restore the levels to those seen in the non-irradiated mice by 4 and 8 weeks after radiation exposure. WI Station examined how the iron regulated RNA binding protein and found that iron regulatory protein 1 (IRP1) had the capacity to control the fate of up to 9 mRNA that contain an iron responsive element (IRE) in their 5’ or 3’ untranslated region. Evidence from studies in mice indicated that the transcription factor HIF2alpha was a major regulator of genes encoding divalent metal transporter I (DMT1), the ferric iron reductase DCytB and the iron exporter ferroportin. These 3 proteins control the apical uptake (DMT1, DCytb) and basolateral export (ferroportin) of iron in the duodenum. IRP1 is the key iron mediator of HIF2alpha mRNA translation. IRP1 is a repressor of HIF2alpha synthesis because it binds to the IRE in HIF2alpha mRNA thereby blocking translation of this mRNA. Loss of IRP1 translationally activates HIF2alpha mRNA. Currently, they are examining the impact of IRP1 deficiency on expression of the HIF2alpha gene targets DMT1, DCytB and ferroportin in the duodenum, as well as the role of IRP1 in other aspects of iron metabolism. NJ Station investigated whether a purified phenolic-enriched raspberry extract would reduce weight gain in a diet-induced obese (DIO) mouse model. For comparison, they used raspberry ketone as a positive control. Eight week-old C57BL/6 male mice were fed high-fat diet (45% fat. 20% protein). Vehicle, raspberry ketone, high and low raspberry extract (REH 2g/kg, REL 0.2mg/kg, respectively) were administered by oral gavage for 24 days, and body weights were recorded daily. They are in the process of analyzing the feeding suppression, meal pattern alterations, and hypothalamic gene expression by phenolic-enriched raspberry extract and raspberry ketone. Their previous experiments found that acute oral dosing of raspberry ketone (200 mg/kg) activates the hindbrain, nucleus of the solitary tract (NTS), as measured by c-fos immunohistochemistry. These findings will provide mechanistic data for uncovering the effects of raspberry ketone and other bioactive phenolic compounds on obesity and related metabolic disorders. Objective 3: Explore the interaction between dietary components and the host metabolome and epigenome. TX Station found that dried plums reduced early colon lesions by 50%, and mitigated distal colon microbiota changes in rats induced by carcinogen-injection. They further discovered several compounds endogenous to plums in the luminal metabolome (both proximal and distal), with several of those compounds being demonstrated in the existing literature to suppress proliferation and enhance apoptosis in colon cancer cells. In addition, there were multiple compounds produced from microbial metabolism of phenolic molecules identified in the luminal contents from the proximal and distal colon of rats provided the plum diet. These molecules have also been demonstrated to protect against carcinogenesis. Additional experiments using dried plums, or compounds isolated from plums have demonstrated effects on bone, as well as colon cancer, demonstrating the potential for systemic benefits of dried plum consumption. Objective 4: Determine how food processing influences chemical composition to affect human health. WA Station has studied the utilization of grape pomace as a functional food component. Grape pomace is a major byproduct of wine and juice industry, rich in polyphenolics with demonstrated preventive effects against cardiovascular disease, inflammatory bowel disease and others. How to effectively utilize this byproduct is a compelling question with huge economic impact. In the study, grape pomace was examined for its potential application in making healthy corn starch based extrusion snack foods. Extrudates with 5% grape pomace and 16% feed moisture at a selected speed resulted in enhanced expansion with substantial retention of total polyphenolic content and total antioxidant activity in the cornstarch extrudates. Furthermore, the protective effect of grape pomace extrudates against reactive oxygen species production in human colonic epithelial cells was further evaluated using polyphenolic extract prepared from grape pomace raw mixes and extrudates. These studies indicate that grape pomace has a potential to be used an adjunctive ingredient in extruded foods providing enhanced nutritional value without negative impacts on quality characteristics. OR Station has been focused on reducing human health risks from food-borne pathogens and environmental contaminants and to transition from preclinical mouse models to actual human studies employing the incredible sensitivity of AMS (attomole sensitivity; they can detect BaP in blood after dosing humans (protocol approved by FDA) at the low femto (1015) gram levels, equivalent to 1 drop of water in 4000 Olympic-size swimming pools. A pending NIH grant will allow them to use human volunteers to assess how consumption of a cruciferous vegetable (1/2 cup Brussels sprouts) night for a week alters the pharmacokinetics of a subsequent oral dose of 14C-BaP.

Publications

<ol> <li>Aleksic B, Bailly S, Draghi M, Pestka JJ, Oswald IP, Robine E, Bailly JD, Lacroix MZ. Production of four macrocyclic trichothecenes by stachybotrys chartarum during its development on different building materials as measured by uplc-ms/ms. Building and Environment 2016, 106, 265-273.</li> <li>Bates MA, Brandenberger C, Langohr II, Kumagai K, Lock AL, Harkema JR, Holian A, Pestka JJ. Silica triggered autoimmunity in lupus-prone mice blocked by docosahexaenoic acid consumption. Plos One 2016, 11: e0160622.</li> <li>Bates MA, Gilley KN, Jackson-Humbles DN, Harkema JR, Holian A, Pestka JJ. Silica-triggered multi-organ autoimmune gene expression in lupus-prone mice is ablated by docosahexaenoic acid consumption. FASEB Journal 2017, 31.</li> <li>Beaver LM, Kuintzle R, Buchanan A, Wiley MW, Glasser ST, Wong CP, Johnson GS, Chang J, Löhr CV, Williams DE, Dashwood RH, Hendrix DA, Ho E. Long Non-Coding RNAs and Sulforaphane: A Target for Chemoprevention and Suppression of Prostate Cancer. Journal of Nutrition Biochemistry 2017, 42:72-83.</li> <li>Bibi S, de Sousa Moraes LF, Lebow N, Zhu MJ. Dietary green pea protects against DSS-induced colitis in mice challenged with high-fat diet. Nutrients 2017, 9: 509</li> <li>Bibi S, Kowalski RJ, Zhang S, Ganjyal GM, Zhu MJ. Stability and functionality of grape pomace Used a nutritive additive during extrusion process. Journal of Food Processing & Technology 2017, 8:680.</li> <li>Bibi S, Kang Y, Du M, Zhu MJ. Maternal high-fat diet consumption enhances offspring susceptibility to DSS-induced colitis in mice. Obesity 2017, 25: 901-908</li> <li>Borresen E, Brown DG, Harbison G, Taylor L, Fairbanks A, O’Malia J, Bazan M, Rao S, Baily S, Wdowik M, Weir TL, Brown RJ, Ryan EP. A randomized-controlled trial to increase navy bean or rice bran consumption in colorectal cancer survivors. Nutrition & Cancer 2016, 68:1269-1280</li> <li>Brown DG, Rao S, Weir TL, O’Malia J, Bazan M, Brown RJ, Ryan EP. Metabolomics investigation of tumors, adjacent colonic mucosa and stool from colorectal cancer patients. Cancer & Metabolism 2016, 4:11.</li> <li>Chen YS, Wang R, Dashwood WM, Löhr C, Williams DE, Ho E, Mertens-Talcott S, Dashwood R. A miRNA signature for an environmental heterocyclic amine defined by a multi-organ carcinogenicity bioassay in the rat. Archives of Toxicology 2017, 91:3415-3425.</li> <li>Doerge DR, Woodling KA, Churchwell MI, Fleck SC, and Helferich WG. Pharmacokinetics of isoflavones from soy infant formula in neonatal and adult rhesus monkeys. Food Chemical Toxicology 2016: S0278-6915.</li> <li>Foster MT, Gentile CL, Cox-York K, Wei Y, Wang D, Estrada A, Reese L, Miller T, Pagliassotti MJ, Weir TL. Fuzhuan tea consumption imparts hepatoprotective effects and alters intestinal microbiota in high saturated fat diet-fed rats. Molecular Nutrition and Food Research 2016, 60:1213-12</li> <li>Gotthardt JD, Bello NT. Meal pattern alterations associated with intermittent fasting for weight loss are normalized after high-fat diet re-feeding. Physiology & Behavior 2017,174: 49-56.</li> <li>Housley L, Hsu A, Beaver LM, Wong CP, Stevens JF, Choi J, Jiang Y, Bella D. Williams DE, Shannon J, Dashwood RH, Ho E. Untargeted metabolic screen reveals changes in human plasma metabolite profiles following consumption of fresh broccoli sprouts. Molecular Nutrition and Food Research. In press.</li> <li>Johnson NB, Deck KM, Nizzi CP, Eisenstein RS. A synergistic role of IRP1 and FBXL5 in coordinating iron metabolism during cell proliferation. Journal of Biology Chemistry 2017, 292: 15976-15989</li> <li>Kang Y, Xue Y, Du M, Zhu MJ. Preventative effects of Goji berry in dextran sulfate sodium-induced colitis. Journal of Nutritional Biochemistry 2017, 40: 70-76.</li> <li>Kunde DA, Chong WC, Nerurkar PV, Ahuja KD, Just J, Smith, JA, Guven, N and Eri, RD Bitter melon extract protects against ER stress in LS174T colonic epithelial cells. BMC Complement Alternative Medicine. 2017, 17: 2.</li> <li>Lee DM, Battson ML, Jarrell, Cox-York K, Foster MT, Weir TL, Gentile CL. Fuzhuan tea reverses arterial stiffening following modest weight gain in mice. Nutrition 2017, 33:266-270.</li> <li>Lemas DJ, Young BE, Baker PR, Tomczik A, Soderborg TK, Hernandez TL, de la Houssaye BA, Robertson CE, Rudolph MC, Ir D, Patinkin ZW, Krebs NF, Santorico SA, Weir TL, Barbour LA, Frank DN, Friedman JE. Alterations in human milk leptin and insulin impact early changes in the infant gut microbiome. American Journal Clinical Nutrition 2016, 103:1291.</li> <li>Madeen EP, Löhr CV, You H, Siddens LK, Krueger SK, Dashwood RH, Gonzalez FJ, Baird WM, Ho E, Bramer L, Waters KM and Williams DE. Dibenzo[def,p]chrysene Transplacental Exposure in Wild-Type, Cyp1b1 Knockout, and CYP1B1 Humanized Mice. Molec. Carcinogenesis 2017, 56:163-171.</li> <li>Monson MS, Cardona CJ, Coulombe RA, Reed KM. Hepatic transcriptome responses of domesticated wild turkey embryos to aflatoxin B1. Toxins 2016, 8: 16.</li> <li>Monson M S, Coulombe RA, Reed KM. Sensitivity and response of poultry to aflatoxin B1 exposure. Agriculture 5 (3) 742-777. 2016, doi:10.3390/agriculture50x000x.</li> <li>Oni EN, Halikere A, Li G, Toro-Ramos AJ, Swerdel MR, Verpeut JL, Moore JC, Bello NT, Bierut LJ, Goate A, Tischfield JA, Pang ZP, Hart RP. Increased nicotine response in iPSC-derived human neurons carrying the CHRNA5 N398 allele. Scientific reports 2016, 6: 34341.</li> <li>Palmoera-Sanchez Z, Watson GW, Wong CP, Beaver LM, Williams DE, Dashwood RH, Ho E. The Phytochemical 3, 3’-Diindolylmethane Decreases Expression of AR-Controlled DNA Damage Repair Genes Through Repressive Chromatin Modifications and is Associated with DNA Damage in Prostate Cancer Cells. Journal of Nutritional Biochemistry 2017, 47:113-119.</li> <li>Pestka JJ, Clark ES, Schwartz-Zimmermann HE, Berthiller F. Sex is a determinant for deoxynivalenol metabolism and elimination in the mouse. Toxins 2017, 9.</li> <li>Reed KM, Mendoza KM Abrahante J, Coulombe RA. Response of the Hepatic Transcriptomes of Domesticated and Wild Turkey to Aflatoxin B1. Presented at International Society of Animal Genetics, Dublin, IR. July 2017.</li> <li>Rendeiro C, Sheriff A, Bhattacharya TK, Gogola JV, Baxter JH, Chen H, Helferich WG, Roy EJ, Rhodes JS. Long-lasting impairments in adult neurogenesis, spatial learning and memory from a standard chemotherapy regimen used to treat breast cancer. Behavioral Brain Research 2016, 315:10-22.</li> <li>Riggs PK, Tedeschi LO, Turner ND, Braga-Neto U, Jayaraman A. The role of “omics” technologies for livestock sustainability. Archive Latinioam Production Animal 2017 25:147-153.</li> <li>Ritchie LE, Taddeo SS, Weeks BR, Carroll RJ, Dykes L, Rooney LW, Turner ND. Impact of novel sorghum bran diets on DSS-induced colitis. Nutrients 2017, 9: E330.</li> <li>Schwartz-Zimmermann HE, Hametner C, Nagl V, Fiby I, Macheiner L, Winkler J, Danicke S, Clark E, Pestka JJ, Berthiller F. Glucuronidation of deoxynivalenol (don) by different animal species: Identification of iso-don glucuronides and iso-deepoxy-don glucuronides as novel don metabolites in pigs, rats, mice, and cows. Archives of Toxicology 2017. In press.</li> <li>Seidel DV, Azcarate-Peril MA, Chapkin RS, Turner ND. Shaping functional microbiota using dietary bioactives to reduce colon cancer risk. Seminars in Cancer Biology 2017, 46:191-204.</li> <li>Sheflin AM, Borresen EC, Kirkwood J, Boot C, Whitney AK, Lu S, Brown RJ, Broeckling CD, Ryan EP, Weir TL. Dietary Supplementation with Rice Bran or Navy Bean Alters Gut Bacterial Metabolism in Colorectal Cancer Survivors. Molecular Nutrition and Food Research 2017, 61:1500905.</li> <li>Sheflin AM, Melby C, Carbonero F, Weir TL. Linking dietary patterns with gut microbial composition and function, Gut Microbes, 2017. 8:113-129</li> <li>Sun X and Zhu MJ. AMP-activated protein kinase: a therapeutic target in intestinal diseases. Open Biology 2017, 7: 170104.</li> <li>Sun X, Yang QY, Rogers CJ, Du M, Zhu MJ. AMPK regulate intestinal differentiation via histone modification of CDX2. Cell Death and Differentiation 2017, 24: 819-831.</li> <li>Tinder AC, Puckett RT, Turner ND, Cammack JA, Tomberlin JK. Bioconversion of sorghum and cowpea by black soldier fly (Hermetia illucens (L.)) larvae for alternative protein production. Journal of Insects as Food and Feed 2017, 3:121-130.</li> <li>Turner ND and Lloyd SK. Association between red meat consumption and colon cancer: A systematic review of experimental results. Experimental Biology & Medicine 2017, 242:813-839.</li> <li>Wang B, Fu X, Zhu MJ, Du M. Retinoic acid inhibits white adipogenesis by disrupting GADD45A mediated Zfp423 DNA demethylation. Journal of Molecular Cell Biology 2017, 9:338-349.</li> <li>Wang B, Fu X, Liang X, Deavila JM, Wang Z, Zhao L, Tian Q, Zhao J, Gomez NA, Trombetta SC, Zhu MJ, Du M. Retinoic acid induces white adipose tissue browning by increasing adipose vascularity and inducing beige adipogenesis of PDGFRa+ adipose progenitors. Cell Discovery 2017, 3:17036.</li> <li>Wang S, Liang X, Yang Q, Fu X, Zhu MJ, Rodgers BD, Jiang Q, Dodson MV, Du M. Resveratrol enhances brown adipocyte formation and function by activating AMP-activated protein kinase (AMPK) a1 in mice fed high-fat diet. Molecular Nutrition and Food Research 2017, 61: 1600746.</li> <li>Whitney AK and Weir TL. Inhibitory activity of Fuzhuan tea fractions against Salmonella enterica and enteric pathogens. Current Topics in Phytochemistry 2016, 13:17-27.</li> <li>Wu W, Zhou H-R, Bursian SJ, Link JE, Pestka JJ. Calcium-sensing receptor and transient receptor ankyrin-1 mediate emesis induction by deoxynivalenol (vomitoxin). Toxicological Sciences 2017, 155:32-42.</li> <li>Wu W, Zhou H-R, Pestka JJ. Potential roles for calcium-sensing receptor (casr) and transient receptor potential ankyrin-1 (trpa1) in murine anorectic response to deoxynivalenol (vomitoxin). Archives of Toxicology 2017, 91:495-507.</li> <li>Xue Y, Du M, Zhu MJ. Quercetin suppresses NLRP3 inflammasome activation in epithelial cells triggered by Escherichia coli O157:H7. Free Radical Biology and Medicine 2017, 108:760-769</li> <li>Xue Y, Zhang D, Du M, Zhu MJ. Dandelion extract suppresses reactive oxidative species and inflammasome in intestinal epithelial cells. Journal of Functional Food 2017 29: 10-18.</li> <li>Xue Y, Du M, Sheng H, Hovde CJ, Zhu MJ. Escherichia coli O157:H7 suppress host autophagy and promote bacterial adhesion via Tir-mediated and cAMP-independent activation of protein kinase A. Cell Death and Discovery 2017, 3, 17055.</li> <li>Xue Y, Zhang H, Sun X, Zhu MJ. Metformin improves ileal epithelial barrier function in interleukin-10 deficient mice. PloS ONE 2016, 11: e0168670</li> <li>Yang G, Bibi S, Du M, Suzuki T, Zhu MJ. Regulation of the intestinal tight junction by natural polyphenols: a mechanistic perspective. Critical Reviews in Food Science and Nutrition 2017, 595: 3830-3839.</li> <li>Yin Q, Tang L, Cai K, Tong R, Sternberg R, Yang X, Dobrucki LW, Borst LB, Kamstock D, Song Z, Helferich WG, Cheng J, Fan TM. Pamidronate Functionalized Nanoconjugates for Targeted Therapy of Focal Skeletal Malignant Osteolysis. Proc Natl Acad Sci U S A. 2016, 113:E4601-9.</li> <li>Zhang X, Cook KL, Warri A, Cruz IM, Rosim M, Riskin J, Helferich W, Doerge D, Clarke R, Hilakivi-Clarke L. Lifetime genistein intake increases the response of mammary tumors to tamoxifen in rats. Clinical Cancer Research 2017. 23: 814-824.</li> <li>Zhao J, Yang Q, Zhang L, Liang X, Sun X, Wang B, Chen Y, Zhu MJ, Du M. AMPKa1 deficiency suppresses brown adipogenesis in favor of fibrogenesis during brown adipose tissue development. Biochemical and Biophysical Research Communications 2017 491: 508-514.</li> <li>Zou T, Yang Q, Wang B, Zhu MJ, Nathanielsz PW, Du m. Resveratrol supplementation to high fat diet-fed pregnant mice promotes brown and beige adipocyte development and prevents obesity in male offspring. Journal of Physiology 2017, 595:1547-1562.</li> </ol>

Impact Statements

12. NJ Station studies on raspberry ketone in weight loss/gain outcomes will provide an unbiased assessment for natural dietary supplements in the market. It can also facilitate a new red raspberries cultivar selection with enhanced bioactive compounds.

Date of Annual Report: 12/04/2018

Report Information

Annual Meeting Dates: 10/04/2018 - 10/05/2018
Period the Report Covers: 10/09/2017 - 10/05/2018

Participants

Harrington, Michael (michael.harrington@colostate.edu) – Colorado State University/WAAESD; Pristos, Cris (pristos@cabnr.unr.edu) – University of Nevada Reno; Chicco, Adam (adam.chicco@colostate.edu) – Colorado State University; Helferich, William (helferic@uiuc.edu) – University of Illinois Urbana Champaign; Williams, David (david.williams@oregonstate.edu) – Oregon State University; Turner, Nancy (ndturner@anr.msu.edu) – Michigan State University; Weir, Tiffany (tiffany.weir@colostate.edu) – Colorado State University; Delgado, Efren (edelgad@nmsu.edu) – New Mexico State University; Majumder, Kaustav (kasutav.majumder@unl.edu) – University of Nebraska Lincoln; Nerurkar, Pratibha (pratibha@hawaii.edu) – University of Hawaii; Chen, Chi (chichen@umn.edu) – University of Minnesota; Eisenstein, Richard (eisenste@nutrisci.wisc.edu) – University of Wisconsin Madison;

Brief Summary of Minutes

Brief summary of minutes of annual meeting (October 4-5, 2018):

Thursday, October 4, 2018

8:30-9:00am - Opening remarks: Mike Harrington, WAAES Director, exiting W4122 Admin. Advisor, provided updates on WAAES and USDA budgets, funding priorities and initiatives. Emphasized importance of carefully crafted activities reports, particularly outcomes and impacts. Introduced Dr. Cris Pristos, NVAES Director and incoming W4122 Admin. Advisor, who provided additional updates and insights on successful practices of the NVAES multistate groups.

9:00am-5:30pm - State Reports/project updates: (30-45 min Presentations/discussion):

9:00 am Bill Helferich – University of Illinois; Health risks and chemistry of abused fry oils

9:30 am David Williams – Oregon State University; Analysis and impact of very low dose benzopyrenes from diet

10:00 am Break

10:30 am Nancy Turner – Michigan State University; Bioactive dietary components that impact colon health.

11:00 am Tiffany Weir – Colorado State University; Benefits of cricket consumption as an alternative protein source; Interaction of gut microbiome and cardiometabolic health

12:00 pm Lunch break

1:30 pm Efren Delgado – New Mexico State University; Detection of food pathogens in food products

2:00 pm Kaustav Majumder – University of Nebraska–Lincoln; Effect bioactive peptides on cardiovascular risk.

2:30 pm Pratibha Nerurkar – University of Hawaii; Benefit of native Hawaiian fruits on diabetes risk.

3:00 pm Break

3:30 pm Chi Chen – University of Minnesota; Influence of food preparation on lipid peroxidation products and metabolites

4:00 pm Adam Chicco – Colorado State University; Links between maternal obesity fetal metabolic programing.

6:00 pm Group dinner – Culinary Institute of America, St. Helena, CA

Friday October 5, 2018:

9:00-10:30am; Business meeting at Calistoga Roastery coffee shop. Covered financial and budgetary information (Mike Harrington and Cris Pristos); Discussed format of final activities report, importance of clear and informative impact statements; Established plans for new collaborations; Voted to hold 2019 Annual Meeting in Estes Park, Colorado the third week of September, hosted by Tiffany Weir and Adam Chicco (Colorado State University), directed by David Williams (Oregon State).

Accomplishments

Objective 1: Examine the effects of phytochemicals and other dietary components on gut microbiota and intestinal function. W4122 scientists in Michgan demonstrated beneficial changes in the colon microbiota of rats when was included in the diet. These studies indicate that consuming a dried plum puree can enhance protection against intestinal disease, and that the benefit is partly derived through their effects on colonic microbiota and metabolic byproducts. W4122 researchers in Colorado have determined that cricket consumption, which is growing in popularity as a sustainable and nutrition al food source, has prebiotic and anti-inflammatory effects in humans. W4122 researchers in Colorado are establishing mechanistic links between gut microbiota and intestinal function and early predictors of cardiovascular disease risk that may lead to novel therapeutic approaches for heart disease prevention. W4122 researchers in Michigan have demonstrated that diets containing certain polyphenolic compounds (derived from dried plums) impact the microbiota and their metabolism, which has significant impacts on multiple pathways involved in inflammation and tumorigenesis involved in the development of colorectal cancers. Objective 2: Identify cellular mechanisms and host molecular targets of beneficial or adverse dietary components that influence human health. In collaboration with Lawrence Livermore National Laboratory and Pacific Northwest National Laboratory, W4122 researchers in Oregon performed the first pharmacokinetic analysis of benzo[a]pyrene (a polycyclic aromatic hydrocarbon, (PAH)) in humans following oral exposure and the impact of food containing high levels of multiple PAHs. With the application of molecular fluorescence spectroscopy for in situ, real-time detection of foodborne pathogens, W4122 scientists in New Mexico are revolutionizing the way we can detect of food pathogens in food products in tissues, thereby helping to better meet food safety requirements in agricultural and industrial food production. W4122 researchers Wisconsin have begun to identify the mechanisms underlying the regulation of dietary iron absorption by IRP1 and HIF2alpha. By elucidating new ways in which dietary iron absorption is controlled it may be possible to develop the means to more safely combat the anemia in production animals and humans as illustrated by our planned experiment using dietary fumarate as a possible means to enhance intestinal HIF2alpha level. W4122 researchers in Wisconsin are identifying how dietary iron absorption and red cell production are controlled which may be of use in humans (anemia of prematurity) or swine (iron deficiency associated with growth) where control (increase) of iron absorption from the diet may ameliorate disease. W4122 researchers in Hawaii have discovered that noni juices, specifically the commercial noni juices, may not be equipotent to ameliorate the development of diabetes suggested by some studies, possibly due the differences in the composition of their bioactive components. Since most of the commercial noni products have not been tested for their beneficial properties in humans, this is an area worth investigating further. W4122 researchers in Colorado have discovered that maternal high-fat feeding alters fetal metabolism in a manner that might predispose offspring to the development of diabetes in late childhood. Teams are using an ovine model to investigate the role of placental fatty acid transport in mediating this response, perhaps leading to novel therapies or dietary interventions that can protect the fetus from a potentially harmful environment during development. W4122 researchers in Colorado have developed new methodology for non-invasive monitoring of metabolism in individual oocytes and embryos, which can predict how well they will develop using assisted reproduction technologies in both humans and animals (e.g., horses and cattle). W4122 researchers from Utah identified candidate miRNAs in the GSTA cluster associated with the observed GST silencing that may underlie the susceptibility phenotype in DT. After a 10-day dietary treatment of AFB1 (300 ppb) in groups of Eastern Wild and Broad Breasted White (DT) turkeys, we obtained livers from 10 animals in each group, also including control birds from both types. Using our turkey liver miRNA-seq dataset, we identified 163 precursor miRNAs with high sequence similarity (BLAST e-score <1e-20) to miRNAs known from other organisms and 13 potentially novel turkey precursor miRNAs that are not similar to known miRNAs but that are also not embedded in annotated repeat sequences or coding sequences, and are not similar to snoRNA, mtRNA, tRNA or other types of RNA. These 176 precursor miRNAs correspond to 256 mature miRNAs expressed at biologically relevant levels and six of the top ten most highly expressed miRNAs are also among the top 10 in chicken liver. Objective 3: Explore the interaction between dietary components and the host metabolome and epigenome. W4122 researchers in Colorado have identified metabolomic signatures associated with high and low fruit and vegetable intake that may be more precise in predicting intake of these foods than the currently used self-report methods. Objective 4: Determine how food processing influences chemical composition to affect human health. W4122 researchers in Illinois found that thermally abused fying oil (TAFO) results in greater invasion and progression of cancerous cells injected into the leg bones of mice. Breast cancer metastasizes to bone in the majority of patients with advanced disease. the effects of thermally abused frying oil on metastasis of BC cells from bone to visceral tissue were investigated. Other activities and achievements: W4122 scientists organized a session on “protein and bio-functions” in the annual meeting of American oil chemist society in 2019. W4122 researchers in New Mexico managed the Southwest Agriculture and Food Security Education project, which graduated students participating in research activities, financed Summer internships with USDA or the food industry for master students in the master’s program, and increased students’ retention rate through direct mentoring. Milestones/Plans for 2019: Dr. Eisenstein will conclude a developmental study in mice to understand how dietary iron absorption and erythropoiesis are controlled by IRP1. Dr. Turner will be continuing her project to explore the impact of baking on the chemopreventive capacity of sorghum, and the impact of diet on radiation-induced changes in apoptosis. We will be initiating our study of inflammation and tumor development in response to diets containing dried plum. We will also be initiating an experiment to determine if the protection conferred by sorghum at the early stages of colon cancer results in fewer tumors. Dr. Majumder will develop clinically applicable dietary-peptide-based therapeutics for the improved treatment of hypertension and other cardiovascular diseases. We plan to continue to determine the impact of IRP1 in controlling dietary iron absorption in mice and to begin to determine if IRP1 control of HIF2alpha is important in the control of dietary iron absorption in neonatal swine. Dr. Nerukar will be continuing her project to explore the impact of fNJ and cNJ on gut microbiome in our HFD-fed mice models. We will also investigate the metabolomics profiles of other functional foods such as bitter melon. Dr, Williams recruited, enrolled and micro-dosed 5 volunteers with 4 doses (25, 50, 100 and 250 ng) of benzo[a]pyrene. The timeline given for the grant funding this project has a target of completing this study with 5 volunteers by November 30, 2019. Dr. Helferich will continue to work on the development of models of breast cancer metastasis and will evaluate the potential of diet and diets containing thermally abused frying oil to modulate development of mammary tumor development. Dr. Weir is exploring the role of cricket chitin in modulating the gut microbiota, particularly whether Bifidobacterium can selectively use chitin as a sole carbon source. Additionally, she plans to do in vivo assays to look at direct effects of chitin and cricket powder on inflammation and barrier function in intestinal epithelial cells. Dr. Weir is also conducting a translational study to look at whether microbiota from humans with vascular dysfunction can recapitulate this phenotype in gnotobiotic animals. Additionally, she will exploring the relation between microbiota and vascular function in a human population. Dr, Weir will apply machine learning and bioinformatics approaches to existing metabolomic dataset to generate preliminary data and establish optimal biofluids/metabolomic platforms for quantifying F&V intake. Dr. Chicco will optimize and apply new methodology for studying oocyte and embryo metabolism in vitro to determine effects of maternal omega-3 fatty acids on embryo health and development.  Dr. Coulombe plans to investigate the functional relevance of candidate miRNAs that could influence human susceptibility to cancer from food components by transfecting turkey hepatocytes with anti-anti miRNAs. Grants awarded or ongoing (18 new or continuing research grants totaling over $10M to study effects of bioactive nutrients on cancer, diabetes, fetal programming by maternal diet, gut health, and cardiovascular risk). NASA. PI: Nancy Turner with Robb Chapkin. Radiation-induced apoptosis avoidance and colon tumorigenesis: Epigenetic regulation in adult stem cells. $888,218 direct/$1,267,846 total costs. Funded 1/7/16 – 1/6/20. NNX15AD64G. USCP. PI: Nancy Turner. Colon cancer chemoprevention with sorghum – impact of cooking. $184,971 direct/total costs. Funded 6/1/15 – 12/31/19. RN001-15. California Dried Plum Board. PI: Nancy Turner with Raymond Carroll. Chemoprotective effects of prunes on colon carcinogenesis. $415,000 direct/total costs. Funded 8/1/18-7/30/21. Grant 580-02. NASA. Co-PI: Nancy Turner with John Lawler (PI) and John Ford. Attenuation of space radiation-induced pro-oxidant and fibrotic signaling in the heart by nutritional and genetic interventions: Adventures in tissue sharing. $104,272 direct/$150,000 total costs. Funded 7/1/17 – 6/30/19. USDA. PI: Nancy Turner with Robb Chapkin, Guoyao Wu and Raymond Carroll. Polyphenol-rich sorghum brans promote colon health via microbial mechanisms. $350,017 direct/$499,999 total costs. Funded 5/15/18 – 5/14/21. 2018-67017-28149. HATCH Supplement (Nerurkar: PI)    09/01/18 to 08/31/20; $80,000; Specialty Crops: From Farm to Human Health OHSU/OSU Cancer Prevention and Control Initiative Pilot Projects- “Zebrafish as a Model for Chemoprevention of T-Cell Lymphoblastic Leukemia (T-ALL)”, $50,000, 1/1/16-12/31/17, Williams PI. NIH, NIEHS, “Benzo[a]pyrene Micro-dosing of Humans: A New Tool for Exposure, Risk Assessment and Prevention”, R01 ES028600-01A1, 01-01-2018-11/30/2022, $2.51 million (total), Williams, PI, Tilton, co-I. Zhu, M. J. (PI), Navarre, R., Chew, B. USDA-NIFA (2018-67017-27517). Pigmented potato restores gut epithelial health impaired by obesity. $500,000 (5/2018 – 5/2021) Du, M., Zhu, M. J. (co-PI). NIH (R01HD067449). Maternal obesity, AMPK and fetal brown adipogenesis. $ 1,561,745 (8/2017-7/2022). Du, A., Y. Lin, W.V. Bernie, and M. J. Zhu (co-PI). USDA-NIFA. Nanomaterials-enhanced multiplex immunosensing device for rapid and sensitive detection of pesticide residues. $500,000. (3/2018 – 2/2021). Zhu, M. J. (PI), Navarre, R., Du, M. Pacific Northwest Potato Council. Pigmented potatoes modulate gut microbiota and improve gut health. $67,239. (9/2016 –8/2019). Zhu, M. J. (PI). National Processed Raspberry Council. Dietary raspberry, gut microbiota and inflammatory bowel disease. $108,844. (10/2014 – 9/2018) Zhu, M. J. (PI), Zhang, H., Chang, E. B. Emerging Research Issues Competitive Grant, WSU. Mechanisms beyond preventive effect of fruit consumption on colorectal cancer. $80,000 (5/2016 – 12/2018). Chicco, PI. NIFA/AFRI Research Grant # 2015-67017-23143 “Elucidating the effects of dietary PUFAs on inflammation and cardiometabolic risk” Period: February 2015- February 2019; Total costs: $499,998 Chicco: PI; Colorado Agricultural Experimental Station (USDA); “Maternal nutrition and fetal metabolic programming: role of placental lipid handling”; Period: May 2017- April 2019; Total costs: $50,000 Chicco Co-PI; Advanced Industries Accelerator Grant (CO Office of Economic Development and International Trade); “A Multi-sensor micro-chamber platform for metabolic screening to improve the quality and efficiency of oocyte and embryo selection in ART clinics” Period: October 2017- September 2019; Total costs: $97,000 Chicco, PI; NIH/NICHD 1R21HD097601-01; “Integrative metabolism of oocyte development and its modulation by maternal diet”09/24/18-08/31/20; $150,000/yr

Publications

Publications: 45 new publication by W4122 members (bolded) in 2017-2018 addressing effects of bioactive nutrients on health and chronic disease risk, as well as basic insights into metabolism, development of new methodology and technologies. Molero, L., Campos, L., Sosa, L., Mao, Y., Flores, N., Delgado, E., Lozano, K. 2018. Development and Characterization of Glandless Cottonseed Meal/Pullulan Fine Fiber Mats. Archives of Nanomedicine, Accepted for publication July 2018. Cuj-Laines, R., Hernández-Santos, B., Reyes-Jaquez, D., Delgado, E., Juarez-Barrientos, J.M., Rodriguez-Miranda, J. 2018. Physicochemical properties of ready-to-eat extruded nixtamalized maize based snacks enriched with grasshopper. International Journal of Food Science & Technology. Accepted for publication. DOI:10.1111/ijfs.13774. Kim, E., G.A. Wright, R.S. Zoh, B.S. Patil, G.K. Jayaprakasha, E.S. Callaway, I. Ivanov, N.D. Turner, R.S. Chapkin. 2018. Establishment of a multi-component dietary bioactive human equivalent dose to delete damaged Lgr5+ stem cells using a mouse colon tumor initiation model. European Journal of Cancer Prevention (In press). Seidel, D.V., S.S. Taddeo, M.A. Azcarate-Peril, R.J. Carroll, and N.D. Turner. Dried plums protect against chemically-induced colon carcinogenesis in Sprague Dawley rats. Journal of Nutrition (Accepted with revision). Nerurkar, P.V.*, Orias, D., Soares, N., Kumar, M. and Nerurkar, V.R. Momordica charantia (Bitter melon) modulates adipose inflammasome gene expression and adipose-gut inflammatory crosstalk in high-fat diet (HFD)-fed mice. J Nutritional Biochem, Submitted revisions Oct 2018 Housley, L, Magaana, A.A., Hsu, A., Beaver, L.M., Wong, C.P., Stevens, J.F., Choi, J., Jiang, Y., Bella, D., Williams, D.E., Maier, C.S., Shannon, J., Dashwood, R.H. and Ho, E. (2018). Untargeted Metabolic Screen Reveals Changes in Human Plasma Metabolite Profiles Following Consumption of Fresh Broccoli Sprouts. Molec. Nutr. Fd. Res., Jan 28, 2018 [Epub ahead of print], PMID: 29377494. Hummel, J.M., Madeen, E.P., Siddens, L.K., Uesugi, S.L., McQuistan, T., Anderson, K.A., Turteltaub, K.W., Ognibene, T.J., Bench, G., Krueger, S.K., Harris, S., Smith, J., Tilton, S.C., Baird, W.M. and Williams, D.E. (2018) Pharmacokinetics of [14C]-Benzo[a]pyrene (BaP) in Humans: Impact of Co-Administration of Smoked Salmon and BaP Dietary Restriction. Fd. Chem. Toxicol. 115:136-147, PMID: 29518434. Williams, D.E. (2018) Association is not Causation (letter). Toxicol. Sci. 164:3.,DOI: 10.1093/toxsci/kfy095. Bibi, S., M. Du, and M. J. Zhu. 2018. Dietary red raspberries reduces colorectal inflammation and carcinogenic risk in DSS-induced colitis in mice. Journal of Nutrition, 148, 667-674. Bibi, S., Y. Kang, M. Du, and M. J. Zhu. 2018. Dietary red raspberries attenuate dextran sulfate sodium-induced acute colitis. Journal of Nutritional Biochemistry, 51:40-46. Sun, X., and M. J. Zhu. 2018. Butyrate inhibits indices of colorectal carcinogenesis via enhancing α-ketoglutarate-dependent DNA demethylation of mismatch repair genes. Molecular Nutrition Food Research, 62: 1700932. Sun, X., M. Du, D. A. Navarre and M. J. Zhu. 2017. Purple potato extract promotes intestinal epithelial differentiation and barrier function by activating AMP-activated protein kinase. Molecular Nutrition and Food Research, 62(4):1700536. Sun, X., Q. Y. Yang, C. J. Rogers, M. Du, and M. J. Zhu. 2017. AMPK regulate intestinal differentiation via histone modification of CDX2. Cell Death and Differentiation, 24: 819-831. Sun, X., X. Fu, M. Du, and M. J. Zhu. 2018. Ex vivo gut culture for tracing gut epithelial development. Open Biology, 8: 170256. Wang, B., F. Zhang, H. Zhang, Z. Wang, Y. Ma, M. J. Zhu, and M. Du. 2017. Alcohol intake aggravates adipose browning and muscle atrophy in cancer associated cachexia. Oncotarget, 8: 100411-100420. Wang, B., Z. Wang, J. M. de Avila, M. J. Zhu, F. Zhang, N. A. Gomez, L. Zhao, Q. Tian, J. Zhao, J. Maricelli, H. Zhang, B. D. Rodgers, and M. Du. 2017. Moderate alcohol intake induces thermogenic brown/beige adipocyte formation via elevating retinoic acid signaling. FASEB Journal, 31:4612-4622. Xing, T., Y. Kang, X. Xu, B. Wang, M. Du, and M. J. Zhu. 2018. Raspberry supplementation improves insulin signaling and promotes brown-like adipocyte development in white adipose tissue of obese mice. Molecular Nutrition and Food Research, 2018, 62:1701035. Zhao, J., Q. Yang, L. Zhang, X. Liang, X. Sun, B. Wang, Y. Chen, M. J. Zhu, and M. Du. 2017. AMPKa1 deficiency suppresses brown adipogenesis in favor of fibrogenesis during brown adipose tissue development. Biochemical and Biophysical Research Communications, 491: 508-514. Zhao, L., T. Zou, N. A. Gomez, B. Wang, M. J. Zhu, and M. Du. (2018). Raspberry alleviates obesity-induced inflammation and insulin resistance in skeletal muscle through activation of AMP-activated protein kinase (AMPK) α1. Nutrition & Diabetes, 8: 39. Zhu, M. J., Kang, Y., Y. Xue, X. Liang, M. P. Gonzalez Carcia, D. Rodgers, D. K. Kagel, M. Du. 2018. Red raspberries suppress NLRP3 inflammasome and attenuate metabolic abnormalities in diet-induced obese mice. Journal of Nutritional Biochemistry, 53:96-103 Zou, T., B. Wang, Q. Yang, J. M. de Avila, M. J. Zhu, J. You, D. Chen, and M. Du. 2018. Raspberry promotes brown and beige adipocyte development in mice fed high-fat diet through activation of AMP-activated protein kinase (AMPK) 1. Journal of Nutritional Biochemistry, 55:157-164. Gentile CL and Weir TL. The gut microbiota at the intersection of diet and health. Science (in press) Shah MS, DeSantis TZ, Yamal JM, Weir TL, Ryan EP, Cope JL, Hollister EB. Re-purposing 16S rRNA gene sequence data for within-case paired tumor, tumor-adjacent biopsy, and fecal samples to identify reproducible microbial markers for colorectal cancer. PLoS One (in press) Soderborg TK, Mulligan CE, Clark SE. Babcock L, Janssen RC, Lemas DL, Johnson LK, Frank DN, Weir TL, Barbour LA, Hernandez TL, Kuhn KA, D’Alessandro A, El Kasim KC, Friedman JE (2018) The Gut Microbiota in Infants of Obese Mothers Increases Hepatic Inflammation and Susceptibility to Obesity and NAFLD in Germ-free Mice. Nature Communications (in press). Stull VJ, Finer E, Bergmans RS, Febvre HP, Longhurst C, Manter DK, Patz J, Weir TL. (2018) Impact of Edible Cricket Consumption and Gut Microbiota in Healthy Adults, a Double-blind Crossover Trial. Scientific Reports. 8, 10762 Lee DM, Battson ML, Jarrell DK, Hou S, Ecton KE, Weir TL, Gentile CG. (2018) SGLT2 inhibition via dapagliflozin improves generalized vascular dysfunction and alters the intestinal microbiota in type II diabetic mice. Cardiovascular Diabetology, 17:62. Gindin M, Febvre HP, Rao S, Wallace TC, Weir TL. (2018) Bacteriophage for Gastrointestinal Health (PHAGE) Study: Evaluating the Safety and Tolerability of Supplemental Bacteriophage Consumption. Journal of the American College of Nutrition. Doi: 10.1080/07315724.2018.1483783. Battson ML, Lee DM, Weir TL, Gentile CG (2018) The gut microbiota as a novel regulator of cardiovascular function and disease. Journal of Nutritional Biochemistry 56: 1-15. Salem G, Al-Feki W, Manter DK, Byrne P, Stromberger ME, Weir TL. (2018) Water stress tolerance of winter wheat (Triticum aestivum L.) genotypes are improved by ACC deaminase bacteria. Rhizosphere 8: 1-7. Cox-York KC, Stoecker E, Hamm AK, Weir TL (2018) Microbial Metabolites in Cancer Promotion or Prevention. In: Microbiome and Cancer (ed. Robertson ES). Springer International Publishing, Cham, Switzerland. Battson ML, Lee DM, Jarrell D, Hou S, Ecton K, Weir TL, Gentile CG (2017) Suppression of Gut Dysbiosis Reverses Western Diet-Induced Vascular Dysfunction. Am J Physiol- Endocrinol & Metabol doi: 10.1152/ajpendo.00187.2017. Guha, S., Majumder, K. (2018). Structural-features of food-derived bioactive peptides with anti-inflammatory activity: A brief review. Journal of Food Biochemistry, DOI: 10.1111/jfbc.12531. Li, Q., Kang, X., Shi, C., Li, Y., Majumder, K., Ninga, Z., Ren, Y. (2018). Moderation of hyperuricemia in rats via consuming walnut protein hydrolysate diet and identification of new antihyperuricemic peptides. Food & Function, 1: 107-116. Chee, M., Majumder, K., Mine, Y. (2017). Intervention of dietary dipeptide gamma-L-glutamyl-L-valine (γ-EV) ameliorates inflammatory response in a mouse model of LPS-induced sepsis. Journal of Agricultural and Food Chemistry, 65: 5953–5960. Majumder, K., Fukuda, T., Zhang, H., Sakurai, T., Taniguchi, Y., Watanabe, H., Mitsuzumi, H., Matsui, T., Mine, Y. (2017). Intervention of isomaltodextrin mitigates intestinal inflammation in a dextran sodium sulfate-induced mouse model of colitis via inhibition of toll-like receptor-4. Journal of Agricultural and Food Chemistry, 65: 810-817. Fukuda, T., Majumder, K., Zhang, H., Matsui, T., Mine, Y. (2017). Adenine has an anti-inflammatory effect through the activation of adenine receptor signaling in mouse macrophage. Journal of Functional Foods, 28: 235-239. Obeidat Y, Catandi GD, Carnevale EC, Chicco AJ, DeMann A, Field S, Chen T. A Multi-Sensor System for Measuring Bovine Embryo Metabolism Biosensors and Bioelectronics in press Pennington ER, Sullivana EM, Fix A, Dadooc S, Zeczycki T, DeSantis A, Schlattner U, Chicco AJ, Brown DA, Shaik SR. Proteolipid domains form in biomimetic and cardiac mitochondrial vesicles and are regulated by cardiolipin concentration but not monolyso-cardiolipin. J Biol Chem in press, 2018. Chicco AJ, Le CH, Gnaiger E, Dreyer HC, D’Alessandro A, Nemkov TG, Hocker AD, Prenni JE, Sindt N, Lovering AT, Subudhi AW, Roach RC. Adaptive remodeling of skeletal muscle energy metabolism in high-altitude hypoxia: Lesson from AltitudeOmics. J Biol Chem 293(18): 6659-6671, 2018. PMID: 29540485 Sloan DB, Warren JM, Williams AM, Wu Z, Abdel-Ghany SE, Chicco AJ, Havird JC. Cytonuclear integration and co-evolution. Nat Rev Genet., In press. PMID: 30018367 Chung DJ, Sparanga, GC, Chicco AJ, Schulte PM. Patterns of mitochondrial membrane remodeling parallel functional adaptations to thermal stress. J Exp Biol, 221:jeb174458, 2018. PMID:29643174 Chung DJ, Healy TM, McKenzie JL, Chicco AJ, Sparagna GC, Schulte PM. Mitochondria, temperature, and the pace of life. Integr Comp Biol. 2018 Apr 30. doi: 10.1093/icb/icy013. In press. PMID: 29718252 Obeidat Y, Evans AJ, Tedjo W, Chicco AJ, Carnevale EM , and Chen T Monitoring of Oocyte/Embryo Respiration Using Electrochemical-Based Oxygen Sensors. Sensors and Actuators B: Chemical, 276 (10):72-81, 2018. Reed, K.M., Mendoza, K.M. Abrahante, J., and Coulombe, R.A. (2017). Response of the Hepatic Transcriptomes of Domesticated and Wild Turkey to Aflatoxin B1. Presented at the Annual Conference of the International Society of Animal Genetics, Dublin, IR. July 2017. Reed, K.M., Mendoza, K.M., Abrahnte, Juan and Coulombe, R.A. (2018) Comparative Response of the Hepatic transcriptomes of Domesticated and Wild Turkey to Aflatoxin B1. Toxins 10 (1) 1-24. doi:10.3390/toxins10010042

Impact Statements

W4122 researchers in Utah have cloned, sequenced and mapped glutathione S-transferase (GST) enzymes known to be important for protecting humans and animals against dietary carcinogens. Because there are numerous dietary compounds that induce protective GSTs, diets can be devised to increase resistance of people and animals to dietary and environmental carcinogens and toxicants. Once an appropriate genetic marker for the AFBO-trapping GST allele has been identified in wild turkeys, we plan to reintroduce resistance into domestic turkeys by backcrossing. An AFB1-resitant turkey would help save the poultry industry millions of dollars lost each year due to contaminating aflatoxins in feeds.

Date of Annual Report: 12/08/2019

Report Information

Annual Meeting Dates: 09/25/2019 - 09/27/2019
Period the Report Covers: 10/01/2018 - 09/30/2019

Participants

Participants Attachment:

W4122 2019 Annual Meeting Report.docx

Brief Summary of Minutes

Minutes Attachment:

W4122 2019 Annual Meeting Report.docx

Accomplishments

Objective 1: Examine the effects of phytochemicals and other dietary components on gut microbiota and intestinal function. The University of California Davis Station tested the hypothesis that diet-induced obesity could be overcome by resistant starch. Resistant starch changed the mouse metabolome and an increase in choline metabolism was seen. Although there was no improvement in weight or insulin resistance, intestinal health was improved in the presence of resistant starch (with high fat diet). Similar observations were made in people. Lactobacillus plantarum is often used as a probiotic and for fermentation of several dietary products. These studies suggest Lactobacillus should be targeted by dietary interventions. The toxic Bacteriocins could be how Lactobacillus impact intestinal health. For example, plantaricin protects human CaCo-2 cells (a model for human small intestine) against disturbance of barrier function which provides protection against absorption of toxins from pathogenic bacteria. The Colorado State University Station has been examining the working hypothesis that Western diet causes derangements to the gut microbiota, which drives changes in intestinal homeostasis and leads to inflammation contributing to vascular dysfunction. When comparing standard and Western diet in mice, protective microbes such as Bifidobacteria were reduced in the western diet. Using antibiotics to kill the microbiota 687 reduced the effects on vascular dysfunction produced by Western diet. When the microbiome was transplanted from mice exhibiting vascular dysfunction to obese mice the result was vascular dysfunction in the recipients.  A reactive hyperemia index was using to assess the degree of dysfunction in humans. Some bacteria (B. longum, A. muciniphila) were associated with a normal reactive hyperemia index. In a translational study, a new human cohort (normal and obese individuals) was recruited and microbiota transplanted into mice (classified by vascular dysfunction). The mice took on the vascular characteristics of the donors but not their weight. Mice that received transplants from obese donors seem to have better vascular function. Further studies suggest the gut microbiome of obese mice enhances ischemic injury and contributes to cardiovascular risk. In a separate study by the CSU station, they found dietary interventions with functional foods like blueberries, aronia berries, red beetroot juice, and microgreens altered oral and gut microbiota and the bioavailability of the bioactive compounds in these foods is influenced by gut and oral microbial communities.   The Station at Michigan State University has found sorghum bran can protect against colon cancer and inflammatory bowel disease models. Polyphenol-free diet led to dramatic changes in the Firmicutes to Bacteroidetes ratio. Cooking of cellulose caused a decrease in short chain fatty acids and butyrate while cooking other brans either did not affect the concentration of short chain fatty acids or increased it slightly. Sumac sorghum bran remains the most protective in both raw and cooked forms.   At the University of Minnesota Station nursery pigs were used to study novel metabolic events in the gastrointestinal (GI) tract after food and feed consumption. Rapeseed is a rich source of choline esters, also present in the seeds of Brassicaceae plants (sinapine is a choline ester of sinapic acid, abundant in rapeseed).  Rapeseed diet increased trimethylamine (TMA), the microbial metabolite of choline, in the large intestine and TMA N-oxide (a marker of cardiovascular disease risk) in the liver and serum. The University of Nebraska Station has been studying the impact of the microbiome and diet on susceptibility to a number of cancers, including colorectal and pancreatic. Dietary components shown to have a major influence on microbial impact and cancer risk include fiber (influences chronic inflammation) and flavonoids. At the Purdue Station the effects of phytochemicals and other dietary components on gut microbiota and intestinal function has been studied. Examination of twelve carbohydrates (monosaccharides, disaccharides, and trisaccharides) were tested as carbon sources for the growth of Escherichia coli LF82 and Bacteroides fragilis from the human gut microbiome. We found different types of carbohydrate selectively effect the metabolism of gut microbes. These carbohydrates could be produced in the intestines as the bacteria break down more complex polysaccharides. Using the growth information, predictions of which types of dietary components will be beneficial for the microbiota can be made for potential probiotic formulations. The Utah State University Station (could not attend) has examined dietary strategies to reduce colonic inflammation and promote gut homeostasis thus reducing the risk of colitis-associated colorectal cancer (CAC). Mice fed Western diets alone had markedly higher colitis and colon tumorigenesis. If mice were fed this same high fat diet, but with 10% black raspberry powder, symptoms of colitis was reduced as well as colon tumor multiplicity and burden. The fecal microbiome profiles in black raspberry diets were distinct; the families Bifidobacteriacea, Streptococcaceae and Turicibacteraceae were markedly altered.    Objective 2: Identify cellular mechanisms and host molecular targets of beneficial or adverse dietary components that influence human health.   The University of Hawaii Station found coffee, the most widely consumed beverage worldwide, when consumed in moderate amounts (up to 4 cups/day) improved mortality rates as well as metabolic abnormalities in humans. Adipocytokines such as leptin and adiponectin play a critical role in chronic diseases. Current studies are in progress to identify the effect of Hawaii-grown coffee on plasma adipocytokine levels among healthy individuals.    The University of Minnesota Station has been studying diets containing Scenedesmus and growth performance (5% increased growth whereas 20% decreased growth).  Among common macronutrient-derived blood biochemicals, serum triacylglycerols and cholesterol levels were dramatically decreased by feeding the 20% Scenedesmus diet.  Metabolomic analysis of liver, serum, feces, and urine samples indicated that Scenedesmus feeding greatly affected metabolites associated with amino acids, lipid, purine, microbial metabolism, and the endogenous antioxidant system. Growth promotion was associated with elevated concentrations of antioxidants, an expanded purine nucleotide cycle, and modified microbial metabolism, while growth suppression was correlated to oxidative stress, disrupted urea cycle, upregulated fatty acid oxidation, and an imbalanced lipidome. These correlations suggest the need to define the dietary inclusion rate threshold for using Scenedesmus and other microalgae supplements as feed ingredients.   The University of Nebraska Station has been studying dietary γ-glutamyl peptide (γ-EV) in the prevention of obesity-associated vascular disorders. The biological activity of dietary γ-glutamyl peptide (γ-EV) was assessed using two vascular endothelial cell lines and one adipocyte line. Intervention with γ-EV reduced inflammation in both adipocyte and vascular endothelial cells by activating the calcium sensing-receptor (CaSR). The results from our absorption study with Caco2 cells indicate that γ-EV can be absorbed, probably via Pep-T1 receptor. Our study indicated that γ-EV pretreatment may reduce development of high blood pressure at a dosage of 500 mg/kg BW.   The Station at Oregon State University has been examined the mechanism of altering the pharmacokinetics of the dietary known human carcinogen, benzo[a]pyrene, by the cruciferous vegetable Brussels sprouts or the supplement derived from Brussels sprouts, 3,3’-diindolylmethane (DIM).  These studies can be conducted in humans with de minimus risk as the dose utilized is lower than the average daily exposure.  This is made possible by collaboration with Lawrence Livermore National Laboratory and their accelerator mass spectrometer that has a sensitivity in the range of attomoles (10-18) to zeptomoles (10-21).  The OSU group has developed a UPLC-MS/MS assay to measure DIM and DIM metabolites in urine in individuals taking the dietary supplement.  The impact of DIM or Brussels sprouts on the absorption, metabolism and excretion of benzo[a]pyrene following oral exposure is being determined.   At the Utah State University Station susceptibility and/or resistance to dietary and environmental carcinogens like aflatoxin B1 (AFB1) has been shown to be governed principally by glutathione S transferase (GST)-mediated detoxification. Domesticated turkeys are highly sensitive to AFB1, whereas wild turkeys are comparatively resistant due to the presence of functional hepatic GSTAs and other possible physiological and immunological interactions. We quantified gene expression following dietary treatment of AFB1 in susceptible and resistant birds. Significantly altered pathways included FXR/RXR and LXR/RXR activation, coagulation system, prothrombin activation, acute phase response, and atherosclerosis signaling. Differential extra-hepatic expression of acute phase protein genes was confirmed by quantitative real time PCR (qRT-PCR) in the original experiment and additional turkey lines. Results demonstrate that wild turkeys possess a capacity to more effectively respond to AFB1 exposure, but these effects were largely the consequence of GST silencing in domestic turkeys.   The Washington State University Station has been studying how dietary raspberry can impact white adipose tissue through activation of AMPK. Dietary raspberry at 5% was effective in preventing obesity and metabolic dysfunction induced by a high fat diet (HFD). HFD inhibited AMP-activated protein kinase (AMPK), a master regulator of energy metabolism. Raspberry supplementation activated AMPK, and formation of brown/beige adipocytes. AMPK knockout mice were employed to show that beneficial effects of raspberry in obesity and metabolic symptoms were AMPK-dependent in mediating browning of white adipose tissue and preventing obesity. Thus raspberry consumption is protective against obesity and metabolic dysfunction associated with consumption of common high energy western diet, and AMPK is a critical mediator for the beneficial effects of raspberry through inducing WAT browning.     Objective 3: Explore the interaction between dietary components and the host metabolome and epigenome.  Note: A number of stations conducted research on the impact of dietary components on the metabolome and microbiome (Objectives 1 and 2) and the interaction between the two.  For the sake of brevity those summaries won’t be repeated here.   The Michigan State University Station Sumac and Black sorghum brans are able to reduce the formation of preneoplastic lesions of colon cancer, relative to a white sorghum bran.  These observations suggest that the polyphenols in Sumac and Black brans may be responsible for the protection, however cooking can reduce polyphenols present in Black and Sumac sorghum brans. To study this further raw and cooked Burgundy, Black, Onyx and Sumac sorghum brans in diets were fed to rats treated with a carcinogen 3 weeks after they began consuming the experimental diets.   Short chain fatty acids (SCFA) were affected by the type of diet consumed.  Cooking had the greatest impact on SCFA produced from the control diet.  Our data suggest that including cooked sorghum brans (especially those from Sumac sorghums) should reduce the formation of preneoplastic lesions of colon cancer. The Utah State University Station has been examining the impact of diet on multi-generation susceptibility to cancer as influenced by the effects of total Western diet on the epigenome.  Mice were bred for three generations, during which they were fed a standard diet (AIN93G) for all generations or the total Western diet for rodents (TWD) during only the F0 generation (ancestral), the F0 through F3 generations (multi-generation), or only the F3 generation (direct).  Colon cancer was initiated in the F3 generation and colon mucosa RNA examined for differential expression of genes (DEG). Interestingly, the DEGs were associated with defense response, immune response, and response to interferon biological process ontology terms. Exposure to the Western diet over multiple generations caused significant DEGs related to immune response in the third generation offspring.  Epigenetic alterations as assessed by DNA methylation is ongoing. In this same study, green tea polyphenols, known to decrease body fat composition, reverse insulin resistance, reduce cardiovascular disease risk, protect against pathogenic bacteria, improve brain function, increase lifespan, and suppress inflammatory processes that contribute to carcinogenesis, were tested as multi-generational chemoprevention agents. Multi-generational exposure to green tea decreased terminal body weight and relative fat mass in F3 females directly exposed to Western diet and decreased tumor multiplicity and burden in both sexes as well as relative spleen mass in females (p=0.0083).  Our results suggest that green tea can reduce colon cancer severity only after cumulative exposure to high-fat Western diets over multiple generations.   Objective 4: Determine how food processing influences chemical composition to affect human health. The University of Hawaii Station has been studying how the eco-environmental differences in geographical regions impact the flavor of cacao. Consumption of polyphenols found in Hawaiian cacao are associated with beneficial/protective effects in susceptibility to metabolic disorders including type II diabetes.  There are four main varieties of the cacao plant and the environment, genetic variation and preparation of the beans and the cacao liquor determine flavor and functional properties (as assessed by metabolomics and lipidomics). These include primary and secondary cacao metabolites. The study still needs to explore how different microbiomes affect the fermentation process. Determining which microbes are present in the natural environment and what functions they are playing is also important. The University of Illinois Station has been studying how multiple uses of frying oil (thermally abused frying oil can impact late-stage breast cancer metastasis. The thermally abused frying oil increased metastasis from breast to lung. In another animal study, when the animals were fed with lard, lard + inhibitor, bacon, or bacon + inhibitor, the bacon-exposed animals showed increased tumors in lungs. The Station at New Mexico State University is working on how food bioengineering technology can enhance quality and yield of agroindustrial products.  Recently, this Station has studied the utilization of agro-industrial by-products as an alternative source of plant protein. Glandless cottonseed meal (GCSM), which has a high protein content, was extruded to obtain aquaculture feed. Tissue analysis of amino acid profiles and fatty acid profiles in shrimp after administration of the GCSM feed showed it to be a superior product, having a higher amount of amino acids and a higher amount of fatty acids across all the diets tested.  GCSM has also exhibited physicochemical characteristics, in vitro and in vivo that are superior when compared to the commercial diet at a fraction of the price for production. Glandless cottonseed meal has the potential not only to feed shrimp but other aquaculture species, however, further research needs to be done to expand its uses as a protein source in feeds. In another study, Jujubes (Ziziphus jujube) has been shown to have a high content of antioxidants, vitamins, and minerals that can be used as food additives. NMSU has studied the effect of coating materials on the microencapsulation efficiency of phenolic compounds extracted from jujube fruit. Microencapsulation of phenolic compounds of jujube was performed, measuring total phenolic content and antioxidant activity at the time of extraction, and after microencapsulation with maltodextrins and gum arabic or glandless cottonseed meal protein as coating materials at different ratios. Jujube has a considerable yield of phenolic compounds with high antioxidant activity that are not stable in solution. Therefore microencapsulation must be done the same day of extraction.

Publications

Bates, M.A, Akbari, P., Gilley, K.N, Jackson-Humbles, D.N, Wagner, J.G, Li, N., Kopec, A.K, Wierenga, K.M, Brandenberger, C., Holian, A., Benninghoff, A., Harkema, J.R, Pestka, J.J, (2018). Dietary Docosahexaenoic Acid Prevents Silica-Induced Development of Pulmonary Ectopic Germinal Centers and Glomerulonephritis in the Lupus-Prone NZBWF1 Mouse. Frontiers in Immunology, 9, article 2002. Bates, M.A, Benninghoff, A., Gilley, K.N, Holian, A., Harkema, J.R, Pestka, J.J, (2019). Mapping of Dynamic Transcriptome Changes Associated with Silica-Triggered Autoimmune Pathogenesis in the Lupus-Prone NZBWF1 Mouse. Frontiers in Immunology, doi: 10.3389/fimmu.2019.00632. Battson ML, Lee DM, Li Puma LC, Ecton KE, Thomas KN, Febvre HP, Chicco AJ, Weir TL, Gentile CL. Gut microbiota regulates cardiac ischemic tolerance and aortic stiffness in obesity. American Journal of Physiology – Heart and Circulatory Physiology – in press. Battson ML, Lee DM, Weir TL, Gentile CG (2018) The gut microbiota as a novel regulator of cardiovascular function and disease. Journal of Nutritional Biochemistry 56:1-15. Brunt VE, Gioscia-Ryan RA, Richey JJ, Zigler MC, Cuevas LM, Gonzalez A, Vazquez-Baeza Y, Battson ML, Smithson AT, Gilley AD, Ackermann G, Neilson AP, Weir TL, Davy KP, Knight RL, Seals DR. (2019) Suppression of the gut microbiome ameliorates ate-related arterial dysfunction and oxidative stress in mice. J Physiol 597:2361-2378 Buckley, M.R., Terry, P.D., Kirkpatrick, S.S., Arnold, J.D., McNally, M.M., Grandas, O.H., Freeman, M.B., Goldman, M.H., Whelan, J., Mountain, D.J.H. (2019) Dietary Supplementation with Zyflamend Poly-Herbal Extracts and Fish Oil Inhibit Intimal Hyperplasia Development Following Vascular Intervention. Nutr. Res. 68:34-44. Cam A., Oyirifi, A.B., Liu, Y., Haschek, W.M., Iwaniec, U.T., Turner, R.T., Engeseth, N.J. and Helferich, W.G. (2019) Thermally abused frying oil potentiates metastasis to lung in murine model of late-stage breast cancer. Cancer Prev. Res. 12:201-210. Chen D, Cheng Y, Peng P, Liu J, Wang Y, Ma Y, Anderson E, Chen C, Chen P, Ruan R. (2019) Effects of intense pulsed light on Cronobacter sakazakii and Salmonella surrogate Enterococcus faecium inoculated in different powdered foods. Food Chem. 296:23-28. Chen H, Peng L, Pérez de Nanclares M, Trudeau MP, Yao D, Cheng Z, Urriola PE, Mydland LT, Shurson GC, Overland M, Chen C. (2019) Identification of Sinapine-Derived Choline from a Rapeseed Diet as a Source of Serum Trimethylamine N-Oxide in Pigs. J Agric Food Chem. 67:7748.  Chen D, Peng P, Zhou N, Cheng Y, Min M, Ma Y, Mao Q, Chen P, Chen C, Ruan R. (2019) Evaluation of Cronobacter sakazakii inactivation and physicochemical property changes of non-fat dry milk powder by cold atmospheric plasma. Food Chem. 290:270-276. Chimimba, J., Pratt, R., Cuellar, M, Delgado, E. (2019) Quality parameters of Masa and Tortillas Produced from Blue Maize (Zea mays sp. mays) Landraces. Journal of Food Science, 84: 213-223. Cox-York KC, Stoecker E, Hamm AK, Weir TL (2019) Chapter 15: Microbial Metabolites in Cancer Promotion or Prevention. pp. 317-346. In: Microbiome and Cancer (ed. Robertson ES). Springer International Publishing, Cham, Switzerland. Cuj-Laines, R., Hernández-Santos, B., Reyes-Jaquez, D., Delgado, E., Juarez-Barrientos, J.M., Rodriguez-Miranda, J. (2018) Physicochemical properties of ready-to-eat extruded nixtamalized maize based snacks enriched with grasshopper. International Journal of Food Science & Technology. 53:1889-1895.   Delgado, E., Valverde-Quiroz, L., Lopez D., Cooke P., Valles-Rosales D., Flores, N. (2019) Characterization of Soluble Glandless Cottonseed Meal Proteins Based on Electrophoresis, Functional Properties and Microscopic Structure. Journal of Food Science. Accepted for publication on July, 2019. Erika del Castillo, Richard Meier, Mei Chung, Devin C. Koestler, Tsute Chen, Bruce J. Paster, Kevin P. Charpentier, Karl T. Kelsey, Jacques Izard, and Dominique S. Michaud.  (2019) The Microbiomes of Pancreatic and Duodenum Tissue Overlap and are Highly Subject Specific but Differ between Pancreatic Cancer and Non-Cancer Subjects Cancer Epidemiology, Biomarkers & Prevention 28(2):370-383. Febvre HP, Rao S, Gindin M, Goodwin NM, Vivanco JS, Manter DK, Wallace TC, Weir TL. (2019) PHAGE: Effects of bacteriophage consumption on gut microbiota, inflammation, and lipid metabolism. Nutrients 11:666. Fiecke C, Kurzer M, Chen C, Csallany A. (2019) The in Vivo Antioxidant Effects of Epigallocatechin-3-Gallate Consumption in Healthy Postmenopausal Women Measured by Urinary Excretion of Secondary Lipid Peroxidation Products. Food and Nutrition Sciences. 10:15-27. Gentile CG and Weir TL (2018) The gut microbiota at the intersection of diet and health. Science 362:776-780. Gindin M, Febvre HP, Rao S, Wallace TC, Weir TL. (2018) Bacteriophage for Gastrointestinal Health (PHAGE) Study: Evaluating the Safety and Tolerability of Supplemental Bacteriophage Consumption. Journal of the American College of Nutrition.  Doi: 10.1080/07315724.2018.1483783. Guha, S., Majumder, K. (2019). Structural-features of Food-derived Bioactive Peptides with Anti-inflammatory Activity: A Brief Review. Journal of Food Biochemistry. 43:e12531. Hamm AK and Weir TL (2019) Spent hops as a source of novel prenylflavonoids for human health. Acta Horticulturae 1236:75-84. Havird JC, Noe GR, Link L, Torres A, Sloan DB, Chicco AJ.  (2019) Do angiosperms with highly divergent mitochondrial genomes have altered mitochondrial function? Mitochondrion 49:1-11. Hintze, K.J, Benninghoff, A., Cho, C.E, Ward, R.E, (2018). Modeling the Western diet for pre-clinical investigations. Advances in Nutrition, 9:263-271. Jeon AB, Ackart DF, Li W, Jackson M, Melander RJ, Melander C, Abramovitch RB, Chicco AJ, Basaraba RJ, Obregón-Henao A. (2019) 2-aminoimidazoles collapse mycobacterial proton motive force and block the electron transport chain. Sci. Rep. 9(1):1513. Kerry L Ivey, Andrew T Chan, Jacques Izard, Aedin Cassidy, Geraint B Rogers and Eric B Rimm. (2019) Role of dietary flavonoid compounds in driving patterns of microbial community assembly mBio. 10(5): e01205-19. Kim, E., G.A. Wright, R.S. Zoh, B.S. Patil, G.K. Jayaprakasha, E.S. Callaway, I. Ivanov, N.D. Turner, R.S. Chapkin.  (2019)  Establishment of a multi-component dietary bioactive human equivalent dose to delete damaged Lgr5+ stem cells using a mouse colon tumor initiation model.  European Journal of Cancer Prevention 28:383-389. Kundu, P., Korol, D.L., Bandara, S., Monaikul, S., Ondera, C.E., Helferich, W.G., Khan, I.A., Doerge, D.R. and Schantz, S.L. (2018) Licorice root components mimic estrogens in an object location task but not an object recognition task. Hormones and Behavior 103:97-106. Kundu, P., Patel, S., Meling, D.D., Deal, K., Gao, L., Helferich, W.G. and Flaws, J.A. (2018) The effects of dietary levels of genistein on ovarian follicle number and gene expression. Reprod. Toxicol. 81:132-139. Lee DM, Battson ML, Jarrell DK, Hou S, Ecton KE, Weir TL, Gentile CG (2018) SGLT2 inhibition via dapagliflozin improves generalized vascular dysfunction and alters the intestinal microbiota in type II diabetic mice. Cardiovascular Diabetology, 17:62. Ma Y, Zhou W, Chen P, Urriola PE, Shurson GC, Ruan R, Chen C. (2019) Metabolomic Evaluation of Scenedesmus sp. as a Feed Ingredient Revealed Dose-Dependent Effects on Redox Balance, Intermediary and Microbial Metabolism in a Mouse Model. Nutrients 11:E1971.  Madeen, E., Siddens, L.K., Uesugi, S., McQuistan, T., Corley, R.C., Smith, J., Waters, K.M., Tilton, S.C., Anderson, K.A., Ognibene, T., Turteltaub, K. and Williams, D.E. (2019) Toxicokinetics of Benzo[a]pyrene in Humans: Extensive Metabolism as Determined by UPLC-Accelerator Mass Spectrometry Following Oral Micro-Dosing. Toxicol. Appl. Pharmacology, 364:97-105. Mine, Y., Jin., Y., Zhang, H., Majumder, K., Zeng, Y., Sakurai, T., Taniguchi, Y., Takagaki, R., Watanabe, H., Mitsuzumi, H. (2019). Therapeutic Effects of Isomaltodextrin in a BALB/c Mouse Model of Egg Allergy. Journal of Functional Foods. 55:305-311. L.F. de Sousa Moraes, X. Sun, M. C. G. Peluzio, and M. J. Zhu. (2019). Anthocyanins /anthocyanidins and colorectal cancer: what is behind the scenes? Critical Reviews in Food Science and Nutrition. 59: 59-71. Neil ES, McGinley JN, Fitzgerald VK, Lauck CA, Tabke JA, Streeter-McDonald MR, Broeckling CD, Weir TL, Foster MT, Thompson HJ. Common bean (Phaseolus vulgaris L.) consumption reduces fat accumulation in a polygenic mouse model of obesity. Nutrients (in press). Nerurkar PV, Orias D, Soares N, Kumar M, Nerurkar VR. (2019) Momordica charantia (bitter melon) modulates adipose tissue inflammasome gene expression and adipose-gut inflammatory crosstalk in high-fat diet (HFD)-fed mice. J Nutr Biochem. 68:16-32. Obeidat Y, Cheng M-H, Catandi G, Carnevale E, Chicco AJ, Chen T. (2019) Design of A Multi-Sensor Platform for Integrating Extracellular Acidification Rate with Multi-Metabolite Flux Measurement for Small Biological Samples. Biosensors and Bioelectronics 15;133:39-47 Obeidat Y, Catandi GD, Carnevale EC, Chicco AJ, DeMann A, Field S, Chen T. (2018) A Multi-Sensor System for Measuring Bovine Embryo Metabolism. Biosensors and Bioelectronics, 126:615-623. Pennington ER, Sullivan EM, Fix A, Dadooc S, Zeczycki T, DeSantis A, Schlattner U, Chicco AJ, Brown DA, Shaik SR. (2018) Proteolipid domains form in biomimetic and cardiac mitochondrial vesicles and are regulated by cardiolipin concentration but not monolyso-cardiolipin. J Biol Chem 293(41):15933-15946. Popova, M., Soboleva, T., Ayad, S., Benninghoff, A., Berreau, L., (2018). A Visible Light-activated Quinolone Carbon Monoxide-releasing Molecule: Prodrug and Albumin-assisted Delivery Enable Anti-cancer and Potent Anti-inflammatory Effects. Journal of the American Chemical Society, 140:9721–9729. Reed, K.M., Mendoza, K.M., and Coulombe, R.A. (2019) Altered Gene Response to Aflatoxin B1 in the Spleens of Susceptible and Resistant Turkeys. Toxins Apr 28;11(5). doi: 10.3390/toxins11050242. Reed, K.M., Mendoza, K.M., and Coulombe, R.A. (2019) Differential Transcriptome Responses to Aflatoxin B1 in the Cecal Tonsil of Susceptible and Resistant Turkeys. Toxins 11:1-19. Reed, K.M., Mendoza, K.M., Abrahnte, Juan and Coulombe, R.A. (2018) Comparative Response of the Hepatic Transcriptomes of Domesticated and Wild Turkey to Aflatoxin B1. Toxins 10:1-24. Rodriguez, D., Benninghoff, A., Aardema, N., Phatak, S., Hintze, K.J, (2019). Basal Diet Determined Long-Term Composition of the Gut Microbiome and Mouse Phenotype to a Greater Extent than Fecal Microbiome Transfer from Lean or Obese Human Donors. Nutrients. 11:1630. Shah MS, DeSantis TZ, Yamal JM, Weir TL,  Ryan EP,  Cope JL, Hollister EB. (2018) <a href="https://peerj.com/manuscripts/27339/">Re-purposing 16S rRNA gene sequence data for within-case paired tumor, tumor-adjacent biopsy, and fecal samples to identify reproducible microbial markers for colorectal cancer</a>. PLoS One <a href="https://doi.org/10.1371/journal.pone.0207002">https://doi.org/10.1371/journal.pone.0207002</a>. Soboleva, T., Esquer, H.J, Anderson, S.N, Berreau, L., Benninghoff, A., (2018). Mitochondrial-Localized Versus Cytosolic Intracellular CO-Releasing Organic PhotoCORMs: Evaluation of CO Effects Using Bioenergetics. ACS Chemical Biology, doi: 10.1021/acschembio.8b00387. Soderborg TK, Mulligan CE, Clark SE. Babcock L, Janssen RC, Lemas DL, Johnson LK, Frank DN, Weir TL, Barbour LA, Hernandez TL, Kuhn KA, D’Alessandro A, El Kasim KC, Friedman JE (2018) The Gut Microbiota in Infants of Obese Mothers Increases Hepatic Inflammation and Susceptibility to Obesity and NAFLD in Germ-free Mice. Nature Communications 9:4462. Song, H., Hughes, J.R., Turner, R.T., Iwaniec, U.T., Doerge, D.R. and Helferich, W.G. (2019) (±)-Equol does not interact with genistein on estrogen-dependent breast tumor growth. Food Chem. Toxicol. 28:110970. Stull VJ, Finer E, Bergmans RS, Febvre HP, Longhurst C, Manter DK, Patz J, Weir TL. (2018) Impact of Edible Cricket Consumption and Gut Microbiota in Healthy Adults, a Double-blind Crossover Trial. Scientific Reports 8, 10762 Wang, H., S. Zhang, Q. Shen, and M. J. Zhu. (2019) A metabolome explanation on beneficial effects of dietary Goji on intestine inflammation. Journal of Functional Food, 53:109-114. Xing, T., Y. Kang, X. Xu, B. Wang, M. Du, and M. J. Zhu. (2018). Raspberry supplementation improves insulin signaling and promotes brown-like adipocyte development in white adipose tissue of obese mice. Molecular Nutrition and Food Research. 62:1701035. Xing, L., Zhang, H., Majumder, K., Zhang, W., Mine, Y. (2019). γ‑Glutamylvaline Prevents Low-Grade Chronic Inflammation via Activation of a Calcium-Sensing Receptor Pathway in 3T3-L1 Mouse Adipocytes. Journal of Agricultural and Food Chemistry. 67 (30):8361-8369.  Xue, Y., M. Du, and M. J. Zhu. (2019). Raspberry extract prevents Escherichia coli O157:H7-induced NLRP3 inflammasome activation. Journal of Functional Food. 56: 224-231. Xue, Y., M. Du, and M. J. Zhu. (2019). Quercetin prevents Escherichia coli O157:H7 adhesion to epithelial cells by suppressing focal adhesions. Frontier in Microbiology. 9: 3278. Yu, L., Wang, L., Mao, C., Duraki, D., Kim, J.E., Huang, R., Helferich, W.G., Nelson, D.R., Park, B.H. and Shapiro, D.J. (2019) Estrogen-independent Myc overexpression confers endocrine therapy resistance on breast cancer cells expressing ERαY537S and ERαD538G mutations. Cancer Lett. 442:373-382. Zhang, Z. Garzotto, M., Davis, E.W. II, Mori, M., Stoller, W.A., Farris, P.E., Wong, C.P., Beaver, L.M., Thomas, G.V., Williams, D.E., Dashwood, R.H., Hendrix, D.A., Ho, E. and Shannon, J. (2019) Sulforaphane bioavailability and chemopreventive activity in men presenting for biopsy of the prostate gland: a randomized control trial. Nutr. Cancer Jun 1:1-14. Zhang, S, Wang, H., and M. J. Zhu. (2019). A sensitive GC/MS detection method for analyzing microbial metabolites short chain fatty acids in fecal and serum samples. Talanta,196: 249-254. Zhao, L., B. Wang, N. Gomez, J. Deavila, M. J. Zhu, and M. Du. (2019). Even a low dose of tamoxifen profoundly induces adipose tissue browning in female mice. International Journal of Obesity, in press. Zhou Y, Zhang N, Arikawa AY, Chen C. (2019) Inhibitory Effects of Green Tea Polyphenols on Microbial Metabolism of Aromatic Amino Acids in Humans Revealed by Metabolomic Analysis. Metabolites 9:96. Zhu, M.J., Kang, Y., Xue, Y., Liang, X., Garcia, M.P.G., Rodgers, D., Kagel, D.R., Du, M. (2018) Red raspberries suppress NLRP3 inflammasome and attenuate metabolic abnormalities in diet-induced obese mice. Journal of Nutritional Biochemistry 53, 96-103. Zou, T., Wang, B., Yang, Q., de Avila, J.M., Zhu, M.J., You, J., Chen, D., Du, M. (2018) Raspberry promotes brown and beige adipocyte development in mice fed high-fat diet through activation of AMP-activated protein kinase (AMPK) alpha1. Journal of Nutritional Biochemistry 55, 157-164.

Impact Statements

The University of California at Davis Station has shown intestinal health was improved by resistant starch even with a high fat diet both in mice and humans and Lactobacillus plantarum, often used as a probiotic and for fermentation of several dietary products, plays an important role in this protection. Colorado State has employed human clinical studies to assess differences in oral bioavailability of two commercial cannabinoid (CBD) preparations and established that CBD reduces inflammatory markers in humans 90 minutes after a single oral dose. CSU has also identified sex-based differences in the oral microbiota that influence chronic response of oral nitrate-reducing bacteria to chronic beetroot juice consumption. Beetroot juice and CBD are both popular dietary supplements and these data are important to inform consumers regarding the bioavailability and bioactivity of these supplements. CSU has established microbiota as a causal factor in vascular dysfunction, an early marker of human cardiovascular disease (CVD). This finding will help identify new modalities for preventing or reversing vascular impairments to reduce the overall risk of later CVD development. W4122 researchers in Colorado have discovered gene-diet interactions that govern the extent to which dietary fats influence heart disease risk. Specifically, they determined that omega-6 fatty acids increase risk of cardiac injury following ischemia only if the FADS2 gene is elevated using genetically-engineered mice. The Colorado State Station hase discovered that maternal high-fat feeding alters fetal metabolism in a manner that might predispose offspring to the development of diabetes in late childhood, and identified a placental enzyme that may be targeted to modify this effect. The University of Hawaii Station has addressed the health disparity in diabetes wherein Native Hawaiians and Pacific Islanders have twice the rate of obesity-associated type 2 diabetes and are five times more likely to die from this chronic disease. This station has shown that polyphenols from native cacao and bitter melon may be effective in protection. The University of Illinois Station has documented than when frying oils are used multiple times it produces by-products that can enhance the formation of lung cancer and metastasis of breast cancer. The Michigan State W4122 researchers have demonstrated that the impact of cooking sorghum bran on chemoprotection from cancer is not uniform, and that some sources are more resistant to thermal processing. Importantly, some bioactive compounds remain equally effective in the raw and cooked state which provides enhanced chemoprotection. The University of Minnesota Station has developed a high throughput metabolomics platform to assess global changes following dietary consumption of rapeseed (produces choline and trimethylamine-N-oxide which is a risk factor for cardiovascular disease), green tea polyphenols and algae in order to predict impacts on human health. At the University of Nebraska-Lincoln Station W4122 researchers have developed potentially clinically effective dietary-peptide-based therapeutics for treatment of hypertension and other cardiovascular diseases. Nebraska has also performed a clinical trial using a food frequency questionnaire to determine the amount and type of flavonoids in their diet. Identification of bacteria that could be driven by class-specific flavonoids, opens the possibility of interventions (probiotic; prebiotic) based on personalized construction of optimal microbiomes. New Mexico State University has found that fishmeal can be substituted with cottonseed meal protein without affecting growth and quality of shrimp. The use of agricultural by-products contributes to reducing the production cost in aquaculture farms. The extracted protein from the cottonseed meal protein has a high foaming capacity comparable to soy protein and can be used as a substitute for soy protein. Oregon State University W4122 research has documented that oral phytochemicals from cruciferous vegetables are rapidly absorbed, metabolized and excreted in urine. This pharmacokinetics analysis will establish the dose and frequency of administration that will produce maximum beneficial effects. The Purdue University Station has documented that certain carbohydrates are utilized by bacteria inhabiting the human intestine and the emergent growth of individual bacteria is markedly different that in mixed culture. This has important implications in probiotic and prebiotic approaches to improve health. Utah State University has shown certain genetic markers can be used to restore AFB1 resistance in domestic breeds of turkeys, and may also shed light on the mechanisms of resistance to AFB1 in animals and humans thereby improving animal health and food safety. Utah State has also shown that dietary intervention study with black raspberries leads to important changes in the composition of the gut microbiome with reduced symptoms of colitis and thus may be a useful functional food for suppression of gut inflammation. Black raspberries may be employed as pre-biotics or pre-biotic/pro-biotic intervention. USU has also shown that the adverse impact of the Western diet can be transgenerational through epigenetic mechanisms. Washington State University W4122 researchers have shown that dietary raspberry, which is enriched with polyphenols and dietary fibers, has beneficial effects on obesity and metabolic dysfunction.

Date of Annual Report: 01/26/2021

Report Information

Annual Meeting Dates: 10/08/2020 - 10/09/2020
Period the Report Covers: 09/27/2019 - 10/08/2020

Participants

Pritsos, Cris (pritsos@cabnr.unr.edu) – University of Nevada Reno; Chicco, Adam (adam.chicco@colostate.edu) – Colorado State University;
Williams, David (david.williams@oregonstate.edu) – Oregon State University;
Turner, Nancy (ndturner@anr.msu.edu) – Michigan State University;
Weir, Tiffany (tiffany.weir@colostate.edu) – Colorado State University;
Delgado, Efren (edelgad@nmsu.edu) – New Mexico State University;
Majumder, Kaustav (kasutav.majumder@unl.edu) – University of Nebraska Lincoln;
Nerurkar, Pratibha (pratibha@hawaii.edu) – University of Hawaii;
Chen, Chi (chichen@umn.edu) – University of Minnesota;
Ilce Medina (ilce@msu.edu) – Michigan State University;
Maria Marco (mmarco@ucdavis.edu)– University of California Davis;
Jacques Izard (jizard@unl.edu)– University of Nebraska;
Ock Chun (ock.chun@uconn.edu)– University of Connecticut ;
Mohit Verma (msverma@purdue.edu)– Purdue University ;
Nick Bello (ntbello@rutgers.edu)– Rutgers University;
Satish Kumar Natarajan (snatarajan2@unl.edu) – University of Nebraska;
Claudia Maier (claudia.maier@oregonstate.edu)– Oregon State University

Brief Summary of Minutes

Minutes Attachment:

W4122 Multistate Group 2020 Annual Meeting Minutes.docx

Accomplishments

Below is a summary of research accomplishments of W4122 research groups representing 13 US states address the 4 primary objective of our multistate project: Objective 1: Examine the effects of phytochemicals and other dietary components on gut microbiota and intestinal function. W4122 researchers in California investigated how proteins and metabolites made by Lactiplantibacillus (Lactobacillus) plantarum contained in fresh, fermented fruits and vegetables and ingested as probiotics can stimulate intestinal epithelial cell repair. In other studies, they studied how L. plantarum can reduce its extracellular environment through extracellular electron transport pathways, which is important in the production of fermented foods and may be useful for modifying the intestinal environment to reduce oxidative stress. W4122 researchers in California continued our investigations to elucidate how resistant starch type 2  (RS2) and other dietary fibers, including whole grains (WG), may reduce the risk for obesity and type 2 diabetes as a consequence of stimulating (and minimizing) growth of certain bacteria in the large intestine. These findings show that future studies may lead to the fine-tuning of dietary fiber composition so that it is more useful for targeting selected bacterial taxa in the intestine that may be needed to achieve a specific and intended health outcome.  W4122 researchers in Nebraska worked in collaboration with Harvard T.H. Chan School of Public Health on statistical methodology to analyze microbiome data concomitantly to dietary data. They collected data from 51,529 men enrolled in the Health Professionals Follow-up Study since 1986 to determine the association between sulfur-metabolizing bacteria in stool and risk of colorectal cancer (CRC) over 26 years of follow-up. Results show that foods associated with higher sulfur microbial diet scores (processed meats and low-calorie drinks and lower consumption of vegetables and legumes) were associated with greater risk of distal colon and rectal cancers, after adjusting for other risk factors.  Further studies are needed to determine how sulfur-metabolizing bacteria might contribute to CRC pathogenesis. W4122 researchers in Indiana investigated a series of twelve carbohydrates (monosaccharides and disaccharides) that are building blocks of human milk oligosaccharides and used them as a carbon source for the growth of Escherichia coli LF82 and Bacteroides fragilis from the human gut microbiome. After obtaining data on the growth of these bacteria in anaerobic conditions, we observed deterministic behavior based on the type of carbon source used, and used a modified logistic model to characterize these growth profiles. Results indicate that bacteria can experience a death phase which is important in determining microbe-microbe interactions. W4122 researchers in Minnesota investigated the biotransformation and metabolic fates of both nutrients and non-nutrients (phytochemicals and microbial metabolites) in the GI tract through LC-MS-based metabolomics analysis. In particular, LC-MS-based untargeted profiling was performed on the lipid extracts from wild rice, white rice, and brown rice, and the phytosterol content of wild rice was further analyzed through the quantification of γ-oryzanol and stigmasterol, illustrating the enrichment of these phytosterols in wild rice due to its unique processing after harvesting. W4122 researchers in Colorado completed several human clinical trials focused on the interaction between dietary supplements and gut health, specifically examining the effects of a Phage-based "prebiotic" in combination with a Bifidobacterium probiotic, a Bifidobacterium probiotic alone, and a novel Bacillus subtilis probiotoc on gut health, immune parameters, inflammation, and gut microbiota composition. Primary findings include 1) evidence that Bacillus subtilis DE111 improved lipid parameters, endothelial function, and modulated immune cell populations both in the basal state and in response to pro-inflammatory stimuli.2) A phage cocktail, PreforPro, when administered with a probiotic, extended benefits to gut health over consumption of the probiotic alone and favorably altered the gut microbiota toward a more anti-inflammatory state, and 3) Bifidobacterium lactis consumption improved several self-assessed parameters of intestinal health over placebo ingestion. W4122 researchers in Colorado in collaboration with Dr. Henry Thompson, established that dry bean and pulse consumption offsets the negative metabolic effects of a high fat diet in diet-induced obesity in rodent models, which may be driven increases in Akermansia muciniphila. This mucin-consuming gut microbial species has been shown to improve metabolic parameters in clinical trials with obese humans as well. Finally, these studies have revealed that there are differences between types of legumes in terms of their impacts on the microbiota and metabolic health. Further research is being done to establish the mechanistic basis of these differences. W4122 researchers in Oregon continued their investigation of Xanthohumol (XN), a prenylated flavonoid found in the flowers of hops, which they have shown to have anti-inflammatory properties, acts as an antioxidants, have chemopreventive properties and improve metabolic syndrome in rodent models. Their new works found that XN modulates the gut microbiome composition, modulates the fecal metabolome including bile acid profiles, and reduces adipose inflammation, which early evidence for effects on liver and brain lipid changes suggestive of effects on neurocognitive performance.  W4122 researchers in Oregon developed chemical fingerprinting methods for the characterization of botanical extracts of Centella asiatica (CA), an edible plant associated with cognitive benefits in pre-clinical models,  to ensure product integrity of extracts. These studies identified caffeoylquinic acids as contributors of bioactivity an confirmed minimal induction or inhibition of a range of P450 enzymes, including CYP3A4, by the CA extract, suggesting a low potential for drug interactions modulated by P450 metabolism.  W4122 researchers in Michigan have demonstrated that diets containing certain polyphenolic compounds (derived from dried plums) impact the microbiota and their metabolism, which has significant impacts on multiple pathways involved in inflammation and tumorigenesis involved in the development of colorectal cancers.  W4122 researchers in New Jersey examined the metabolic effects of raspberry ketone (RK)on preventing diet-induced obesity, specifically examining the absorption, metabolism, and distribution of acute orally administered RK  in mice. Results indicate that RK is highly bioavailable, rapidly metabolized, and exhibits significantly different pharmacokinetic behaviors between obese and control mice. In other experiments, they determined that RK has dose-differential effects on feeding patterns and cardiovascular function, which needs consideration as it is used as a nutraceutical for weight control for obesity. In particular, results indicated a dose-dependent feeding suppression with acute RK, but doses that reliable suppress food intake are associated with pathological changes. Objective 2: Identify cellular mechanisms and host molecular targets of beneficial or adverse dietary components that influence human health. and Objective 3: Explore the interaction between dietary components and the host metabolome and epigenome. W4122 researchers in Connecticut examined the relationship between citrus consumption and cutaneous melanoma risk among 56,205 Caucasian postmenopausal women in the Women’s Health Initiative. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of melanoma by citrus intake level. During a mean follow-up of 15.7 years, 956 incident melanoma cases were documented. In multivariable adjusted models, the HR (95% CI) for melanoma was 1.12 (0.91, 1.37) among the highest citrus consumers (1.5+ servings/day of fruit or juice) versus the lowest (<2 servings/week), 0.95 (0.76, 1.20) among the highest citrus fruit consumers (5+ servings/week) versus non-consumers, and was 1.13 (0.96, 1.32) for the highest citrus juice consumers (1+ servings/day) versus the lowest (<1 serving/week). In stratified analyses, an increased melanoma risk associated with citrus juice intake was observed among women who spent the most time outdoors in summer as adults; the HR for the highest versus lowest intake was 1.22 (1.02, 1.46) (p trend = 0.03). W4122 researchers in Colorado completed two pilot clinical studies exploring the pharmacokinetics of different cannabidiol preparations and the individual factors (such as body composition) that may influence the absorption and clearance of these compounds in humans. Specifically, we found that water soluble preparations, when consumed as a beverage, had increased bioavailability over lipid soluble preparations, and that fat free mass was a significant predictor of time to peak concentration for the preparation that had the greatest Cmax. W4122 researchers in Nebraska evaluated the benefits of dietary γ-glutamyl peptides in the prevention of vascular disorders. Based on evidence that food-derived dietary bioactive peptides exhibit antioxidant and anti-inflammatory properties, and the well-established role of chronic inflammation in obesity-associated vascular diseases, studies were performed to test the biological activity of dietary γ-glutamyl peptide (γ-EV) in vascular endothelial cells (HAoEC: Human Aortic Endothelial Cells). Results indicate that γ-EV reduce inflammation in by activating the calcium sensing-receptor (CaSR), and can be absorbed via Pep-T1 receptor. W4122 researchers in Nebraska have developed a green chemistry based scalable extraction method to isolate γ-glutamyl peptides from Nebraskan Great Northern Beans. W4122 researchers in Nebraska evaluated the effects of omega-3 Fatty Acid-Derived Resolvin D2 on placental trophoblast activities, which is important for pregnancy and healthy neonatal development. One mechanism by which omega-3 fatty acids exert their protective effects is through serving as substrates for the generation of specialized pro-resolving lipid mediators (SPM) that potently limit and resolve inflammatory processes. Researchers identified GPR18, an omega-3 fatty acid receptor, in placental vascular smooth muscle and extravillous trophoblasts, and determined that its stimulation with RvD2 led to significantly altered responsiveness to inflammatory stimulation in human umbilical artery smooth muscle cells and placental trophoblasts. Taken together, these findings establish a role for SPM actions in human placental tissue. W4122 researchers in Hawaii are studying the effect of Hawaii-grown coffee on plasma adipocytokine levels among healthy individuals. W4122 researchers in Tennessee, in collaboration with the vascular surgeons of the University of Tennessee Medical Center, started a clinical trial investigating the impact of a combination of dietary bioactives in the stability of peripheral stents. This work was based on a preclinical model of vascular injury (Buckley et al. Nutr Res 68:34-44.) However, the Clinical Trial has been suspended since March 1, 2020, due to Covid-19. W4122 researchers in Minnesota are developing methods to discover unreported metabolic events in diverse biological samples, including urine, blood, other biofluids, and tissue samples through LC-MS-based metabolomic analysis. In a recent study, six thermally oxidized soybean oils (OSO) with a wide range of quality measures were prepared under different processing temperatures and processing durations. Broilers and nursery pigs were randomly assigned to diets containing either unheated control soybean oil or one of six OSO. Animal performance was determined by measuring body weight gain, feed intake, and gain to feed ratio, and correlated with chemical profiles of OSOs, revealing several associations with growth performance in both broilers and pigs.   W4122 researchers in Oregon, in collaboration with Lawrence Livermore National Laboratory and Pacific Northwest National Laboratory, analyzed benzo[a]pyrene (a polycyclic aromatic hydrocarbon, (PAH)) in humans following oral exposure in an ongoing effort to determine the impact of food containing high levels of multiple PAHs on human health. W4122 researchers in Colorado are investigating how maternal high-fat feeding and omega-3 fatty acid supplementation alters fetal metabolism in a manner that may influence the susceptibility of offspring to developing obesity or diabetes in late childhood.  Teams are using an ovine model to investigate the role of placental fatty acid transport in mediating this response, perhaps leading to novel therapies or dietary interventions that can protect the fetus from a potentially harmful environment during development. Objective 4: Determine how food processing influences chemical composition to affect human health. W4122 researchers in New Mexico are evaluating the use of hydrolyzed food waste as an economical and sustainable alternative to be employed as a culture medium and add value to Agroindustrial byproducts. The proposed technology is also useful on obtaining specific heterologous proteins, single-cell proteins and single-cell oils derived from the yeast.  In this work, hydrolyzed agro-industrial wastes from chili, sugarcane bagasse and GCSM are used as liquid culture mediums to grow the modified yeast Yarrowia lipolytica to express oleosin from glandless cottonseed protein. W4122 researchers in Hawaii used metabolomics and lipidomics approach to identify environmental effects not only on polyphenols but also signatures of secondary metabolites of cacao, a polyphenol are associated with several health benefits including improving metabolic disorders.

Publications

There were 71 new publications by W4122 members in 2019-2020 period, addressing the effects of bioactive nutrients on health and chronic disease risk, basic insights into nutrient metabolism, and the development of new methodology and technologies for studying these processes in humans and biological model systems.  Publcations are listed below with W4122 group members in boldfaced text. Riley L. Hughes, Mary E. Kable, Maria L. Marco, Nancy L. Keim, 2019. The role of the gut microbiome in predicting response to diet and the development of precision nutrition models. Part II: Results. Advances in Nutrition. Nov 1;10(6):979-998. Solomon A. Mekonnen, Daniel Merenstein, Claire M. Fraser, and Maria L. Marco. 2020. Molecular mechanisms of probiotic prevention of antibiotic-associated diarrhea. Current Opinion in Biotechnology. 61:226-234 Zachary A. Bendiks, Knud E.B. Knudsen, Michael J. Keenan, and Maria L. Marco. 2020. Conserved and variable responses of the gut microbiome to resistant starch type 2. Nutrition Research. 77:12-28. doi: 10.1016/j.nutres.2020.02.009 Derrick Risner, Maria L. Marco, Sara A. Pace, and Edward S. Spang. 2020. The potential production of the bioactive compound pinene using whey permeate. Processes. 8(3), 263 Paraiso IL, Revel JS, Choi J, Miranda CL, Lak P, Kioussi C, Bobe G, Gombart AF, Raber J, Maier CS, Stevens JF. Targeting the Liver-Brain Axis with Hop-Derived Flavonoids Improves Lipid Metabolism and Cognitive Performance in Mice. Mol Nutr Food Res. 2020 Aug;64(15):e2000341. doi: 10.1002/mnfr.202000341. Epub 2020 Jul 6. PMID: 32627931. Logan IE, Bobe G, Miranda CL, Vasquez-Perez S, Choi J, Lowry MB, Sharpton TJ, Morgun A, Maier CS, Stevens JF, Shulzhenko N, Gombart AF. Germ-Free Swiss Webster Mice on a High-Fat Diet Develop Obesity, Hyperglycemia, and Dyslipidemia. Microorganisms. 2020 Apr 5;8(4):520. doi:10.3390/microorganisms8040520. PMID: 32260528; PMCID: PMC7232377. Zhang Y, Bobe G, Revel JS, Rodrigues RR, Sharpton TJ, Fantacone ML, Raslan K, Miranda CL, Lowry MB, Blakemore PR, Morgun A, Shulzhenko N, Maier CS, Stevens JF, Gombart AF. Improvements in Metabolic Syndrome by Xanthohumol Derivatives Are Linked to Altered Gut Microbiota and Bile Acid Metabolism. Mol Nutr Food Res. 2020 Jan;64(1):e1900789. doi: 10.1002/mnfr.201900789. Epub 2019 Dec 15. PMID: 31755244; PMCID: PMC7029812. Matthews DG, Caruso M, Alcazar Magana A, Wright KM, Maier CS, Stevens JF, Gray NE, Quinn JF, Soumyanath A. Caffeoylquinic Acids in Centella Asiatica Reverse Cognitive Deficits in Male 5XFAD Alzheimer's Disease Model Mice. Nutrients. 2020 Nov 13;12(11):3488. doi: 10.3390/nu12113488. PMID: 33202902; PMCID: PMC7698091. Wright KM, Magana AA, Laethem RM, Moseley CL, Banks TT, Maier CS, Stevens JF, Quinn JF, Soumyanath A. Centella asiatica Water Extract Shows Low Potential for Cytochrome P450-Mediated Drug Interactions. Drug Metab Dispos. 2020 Oct;48(10):1053-1063. doi: 10.1124/dmd.120.090860. Epub 2020 Jun 24. PMID: 32581050; PMCID: PMC7543484. Alcazar Magana A, Wright K, Vaswani A, Caruso M, Reed RL, Bailey CF, Nguyen T, Gray NE, Soumyanath A, Quinn J, Stevens JF, Maier CS. Integration of mass spectral fingerprinting analysis with precursor ion (MS1) quantification for the characterisation of botanical extracts: application to extracts of Centella asiatica (L.) Urban. Phytochem Anal. 2020 Nov;31(6):722-738. doi: 10.1002/pca.2936. Epub 2020 Apr 12. PMID: 32281154; PMCID: PMC7587007. Selamassakul O, Laohakunjit N, Kerdchoechuen O, Yang L, Maier CS. Bioactive  peptides from brown rice protein hydrolyzed by bromelain: Relationship between biofunctional activities and flavor characteristics. J Food Sci. 2020 Mar;85(3):707-717. doi: 10.1111/1750-3841.15052. Epub 2020 Feb 11. PMID: 32043604. Song Z, Pearce MC, Jiang Y, Yang L, Goodall C, Miranda CL, Milovancev M, Bracha S, Kolluri SK, Maier CS. Delineation of hypoxia-induced proteome shifts in osteosarcoma cells with different metastatic propensities. Sci Rep. 2020 Jan 20;10(1):727. doi: 10.1038/s41598-019-56878-x. PMID: 31959767; PMCID: PMC6971036. Preston GW, Yang L, Phillips DH, Maier CS. Visualisation tools for dependent peptide searches to support the exploration of in vitro protein modifications. PLoS One. 2020 Jul 8;15(7):e0235263. doi: 10.1371/journal.pone.0235263. PMID: 32639981; PMCID: PMC7343161. Magana AA, Reed RL, Koluda R, Miranda CL, Maier CS, Stevens JF. Vitamin C Activates the Folate-Mediated One-Carbon Cycle in C2C12 Myoblasts. Antioxidants (Basel). 2020 Mar 5;9(3):217. doi: 10.3390/antiox9030217. PMID: 32150984; PMCID: PMC7139526. Maruthamuthu, M.K., Raffiee, A.H., De Oliveira, D.M., Ardekani, A.M.,, Verma, M.S. (2020) Raman spectra-based deep learning – a tool to identify microbial contamination MicrobiologyOpen (in press). Yildirim, A., Grant, J.C., Siamak, S.E., Lee, W., Maruthamuthu, M.K., Verma, M., Sutherland, J.W., Cakmak, M. (2020) Roll‐to‐Roll (R2R) Production of Large‐Area High‐Performance Piezoelectric Films Based on Vertically Aligned Nanocolumn Forests Advanced Materials Technologies. DOI: 10.1002/admt.202000553. Maruthamuthu, M.K., Rudge, S.R., Ardekani, A.M., Ladisch, M.R., Verma, M.S. (2020) Process Analytical Technologies and Data Analytics for Manufacture of Monoclonal Antibodies Trends in Biotechnology. DOI: 10.1016/j.tibtech.2020.07.004. Waimin, J.F.,§ Nejati, S.,§ Jiang, H., Qiu, J., Wang, J., Verma, M.S., Rahimi, R. (2020) Smart Capsule for Non-invasive Sampling and Studying of the Gastrointestinal Microbiome RSC Advances; 10: 16313-16322. DOI: 10.1039/C9RA10986B Zhao D, Yuan B, Kshatriya D, Polyak A, Simon JE, Bello NT, Wu Q. Influence of Diet-Induced Obesity on the Bioavailability and Metabolism of Raspberry Ketone (4-(4-Hydroxyphenyl)-2-Butanone) in Mice. Mol Nutr Food Res. 2020 Apr;64(8):e1900907. doi: 10.1002/mnfr.201900907. Epub 2020 Feb 25. PMID: 32052560; PMCID: PMC7329366. Yuan B, Zhao D, Kshatriya D, Bello NT, Simon JE, Wu Q. UHPLC-QqQ-MS/MS method development and validation with statistical analysis: Determination of raspberry ketone metabolites in mice plasma and brain. J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Jul 15;1149:122146. doi: 10.1016/j.jchromb.2020.122146. Epub 2020 May 19. PMID: 32474352; PMCID: PMC7391222. Kshatriya D, Hao L, Li X, Bello NT. Raspberry Ketone [4-(4-Hydroxyphenyl)-2-Butanone] Differentially Effects Meal Patterns and Cardiovascular Parameters in Mice. Nutrients. 2020 Jun 11;12(6):1754. doi: 10.3390/nu12061754. PMID: 32545402; PMCID: PMC7353175. Hao L, Kshatriya D, Li X, Badrinath A, Szmacinski Z, Goedken MJ, Polunas M, Bello NT. Acute feeding suppression and toxicity of raspberry ketone [4-(4-hydroxyphenyl)-2-butanone] in mice. Food Chem Toxicol. 2020 Sep;143:111512. doi: 10.1016/j.fct.2020.111512. Epub 2020 Jun 19. PMID: 32565406; PMCID: PMC7483346. Wang Y, Miller JW, Bello NT, Shapses SA. Low-vitamin-D diet lowers cerebral serotonin concentration in mature female mice. Nutrition Research. 2020 Sep;81:71-80. doi: 10.1016/j.nutres.2020.07.006. Epub 2020 Jul 24. PMID: 32920521. Muthuraj PG, Natarajan, SK. Fetal Programming in Maternal Obesity. Diabesity 2020; 6(3): 36-39. DOI:10.15562/diabesity.2020.71 Review Thoene M, Van Ormer M, Lyden E, Thompson M, Yuil-Valdes A, Natarajan SK, Mukherjee M, Nordgren TM, Furtado, Anderson-Berry A, Hanson C, Snowden J. Inflammatory Compounds and Fat-Soluble Nutrients in Mother-Infant Dyads at Time of Delivery. Pediatr Res (2020). In Press Liu B, Lu Y, Chen X, Muthuraj PG, Li X, Pattabiraman M, Zempleni J, Kachman SD, Natarajan SK, Yu J. Protective Role of Shiitake Mushroom-Derived Exosome-Like Nanoparticles in D-Galactosamine and Lipopolysaccharide-Induced Acute Liver Injury in Mice. Nutrients. 2020 Feb 13;12(2):477. doi: 10.3390/nu12020477. PMID: 32069862. Thoene M, VanOrmer M, Yuil-Valdes AG, Bruett T, Natarajan SK, Mukherjee M, Thompson M, Nordgren TM, Lippevelde WV, Overby, NC, Adu-Bonsaffoh K, Anderson-Berry A, Hanson C. Fat-Soluble Nutrients and Omega-3 Fatty Acids as Modifiable Factors Influencing Preterm Birth Risk. Placenta. 2020 Sep 1; 98:38-42. doi: 10.1016/j.placenta.2019.12.002. PMID: 33039030. Ulu A, Sahoo PK, Yuil-Valdes AG, Mukherjee M, VanOrmer M, Muthuraj PG, Thompson M, Anderson-Berry A, Hanson CK, Natarajan SK*, Nordgren TM*. Omega-3 fatty acid-derived resolving D2 regulates human placental vascular smooth muscle and extravillous trophoblast activities. Int. J. Mol. Sci. 2019 Sep 7;20(18):4402. doi: 10.3390/ijms20184402. PMID: 31500240. *Co-corresponding author. Johnson SA, Prenni J, Heuberger AL, Isweiri H, Chaparro J, Newman S, Uchanski M, Omerigic H, Michell K, Bunning M, Foster MT, Thompson HJ, Weir TL. Comprehensive Evaluation of Metabolites and Minerals in Six Microgreen Species and the Influence of Maturity. Current Development in Nutrition (in press) Weir TL, McGinley JN, Neil ES, Thompson HJ (2020) Effect of pulse consumption on obesity and the metagenome, Proceedings of the 1st International Conference on Nutrients- Nutrition and Microbiota Effects on Chronic Disease. doi:10.3390/IECN2020-07009 Soderborg TK, Carpenter C, Janssen RC, Weir TL, Young BE, Krebs NF, Hernandez TL, Barbour LA, Frank DN, Kroehl, M, Friedman JE. (2020) Gestational diabetes is uniquely associated with altered early seeding of the infant gut microbiota. Front Endocrinol doi:10.3389/fendo.2020.603021 Grubb DS, Wrigley SD, Freedman KE, Wei Y, Vazquez AR, Trotter RE, Wallace TC, Johnson SA and Weir TL (2020) PHAGE-2 Study: Supplemental Bacteriophages Extend Bifidobacterium animalis subsp. lactis BL04 Benefits on Gut Health and Microbiota. Nutrients 12, 2474; doi:10.3390/nu12082474 Weir TL, Trikha SRJ, Thompson HJ (2020) Diet and Risk of Cancer Reduction: The Role of Diet-Microbiota Interactions and Microbial Metabolites. Seminars in Cancer Biology DOI: 10.1016/ j.semcancer.2020.06.007 Trotter RE, Vazquez AR, Grubb D, Freedman KE, Wei Y, Jones S, Gentile CL, Melby CL, Johnson SA, Weir TL (2020) Examining the Impact of Probiotic Supplement Intake on Endothelial Function and Lipid Metabolism in Healthy Adults. Beneficial Microbes 11 (7): 621-630. Lee DM, Ecton K, Trikha SR, Wrigley SD, Thomas K, Battson M, Wei Y, Johnson SA, Weir TL, and Gentile CL. (2020) Microbial Metabolite Indole-3-Propionic Acid Supplementation Does Not Protect Mice from the Cardiometabolic Consequences of a Western Diet. Am J Physiol-Gastro Liver Physiol doi.org/10.1152/ajpgi.00375.2019 Hobbs JM, Vazquez AR, Remijan ND, Trotter RE, McMillan TV, Freedman K, Wei Y, Arnold OR, Wolfe LM, Johnson SA, and Weir TL (2020) Evaluation of Pharmacokinetics and Acute Anti-Inflammatory Potential of Two Oral Cannabidiol (CBD)Preparations. Phytotherapy Research DOI:10.1002/ptr.6651 Michell KA*, Isweiri H, Newman SE, Bunning M, Bellows LM, Dinges ME*, Grabos LE*, Rao S, Foster MT, Heuberger AL, Prenni JE, Thompson HJ, Uchanski ME, Weir TL, Johnson SA (2020) Microgreens for the Masses: Exploring Consumer Acceptance and Sensory Perceptions of an Emerging Functional Food Crop. Journal of Food Science McGinley JN, Fitzgerald VK, Neil ES, Omerigic HM, Heuberger AL, Weir TL, McGee R, Vandermark G, Thompson HJ. (2020) Pulse Crop Effects on the Gut Microbial Populations, Intestinal Function, and Adiposity in a Mouse Model of Dietary Induced Obesity. Nutrients 12:593; doi: 10.3390/nu12030593 Thompson HJ, McGinley JN, Neil ES, Weir TL. (2020) Effect of common bean consumption on the gut associated microbiome in an in vivo screening model for breast cancer. Proceedings of the 1st International Conference on Nutrients-Nutrition and Microbiota Effects on Chronic Disease. doi: 10.3390/IECN2020-07008. Puckett, D.L., Alani, D.S., Chahed, S., Frankel, V.D., Alquraishi, M., Donohoe, D.R., Voy, B.H., Whelan, J., and Bettaieb, A. 2020. The cross-talk between PKA and JNK mediates the anti-adipogenic potential of Zyflamend, a unique herbal blend. Adipocyte 9:454-471. (doi:10.1080/21623945.2020.1803642) Puckett, D.L., Chahed, S., Alani, D.S., Donohoe, D.R., Whelan, J., and Bettaieb, A. 2020.  Zyflamend Induces Apoptosis in Pancreatic Cancer Cells via Modulation of the JNK Pathway. 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Antibiotics  9: 463 (2020) Yuan J, Kerr BJ, Curry SM, Chen C, Identification of C9-C11 unsaturated aldehydes as prediction markers of growth and feed intake for non-ruminant animals fed oxidized soybean oil. J Anim Sci Biotechnol. 11: 49 (2020) Chen D, Wiertzema JR, Peng P, Cheng Y, Wang Y, Liu J, Ma Y, Mosher W, Kang M, Min M, Chen P, Baumler DJ, Chen C, Lee L, Vickers Z, Feirtag J, Ruan R. Catalytic intense pulse light inactivation of Cronobacter sakazakii and other pathogens in non-fat dry milk and wheat flour. Food Chem. 332:127420 (2020) Fritsch J, Garces L, Quintero MA, Pignac-Kobinger J, Santander AM, Fernández I, Ban YJ, Kwon D, Phillips MC, Knight K, Mao Q, Santaolalla R, Chen XS, Maruthamuthu M, Solis N, Damas OM, Kerman DH, Deshpande AR, Lewis JE, Chen C, Abreu MT, Low-fat, High-fiber Diet Reduces Markers of Inflammation and Dysbiosis and Improves Quality of Life in Patients With Ulcerative Colitis. Clin Gastroenterol Hepatol. 20: S1542-3565 (2020) Sathe AG, Tuite P, Chen C, Ma Y, Chen W, Cloyd J, Low WC, Steer CJ, Lee BY, Zhu XH, Coles LD, Pharmacokinetics, Safety, and Tolerability of Orally Administered Ursodeoxycholic Acid in Patients With Parkinson's Disease—A Pilot Study, J Clin Pharmacol. 60: 744-750 (2020) Cui W, Sathyanarayan A, Lopresti M, Aghajan M, Chen C, Mashek DG. Lipophagy-derived fatty acids undergo extracellular efflux via lysosomal exocytosis. Autophagy. 19: 1-16 (2020) An J, Liu J, Liang Y, Ma Y, Chen C, Cheng Y, Peng P, Zhou N, Zhang R, Addy M, Chen P, Liu Y, Huang G, Ren D, Ruan R. Characterization, bioavailability and protective effects of phenolic-rich extracts from almond hulls against pro-oxidant induced toxicity in Caco-2 cells. Food Chem. 322:126742 (2020) Nerurkar PV*, Orias D, Soares N, Kumar M, Nerurkar VR. (2019) Momordica charantia (bitter melon) modulates adipose tissue inflammasome gene expression and adipose-gut inflammatory crosstalk in high-fat diet (HFD)-fed mice. J Nutr Biochem. 2019 Jun;68:16-32. doi: 10.1016/j.jnutbio.2019.03.003. Epub 2019 Mar 23. PMID: 31005847 Kar, A., Wei, X., Majumder, K., Eskridge, K., Handa, A., Subbiah, J. (2020). Effect of traditional and radiofrequency assisted thermal processing on the gel firmness of egg white powder. LWT-Food Science and Technology, 133: 110091. Guha, S., Paul, C., Alvarez, S., Mine., Y., Majumder, K*. (2020). Dietary γ-glutamyl valine (γ-EV) ameliorates TNF-α induced vascular inflammation via endothelial calcium-sensing receptor (CaSR). Journal of Agricultural and Food Chemistry, 68: 9139. Mine, Y., Majumder, K., Jin, Y., Zheng, Y. (2020). Chinese Sweet Tea (Rubus suavissimus) Polyphenols Attenuate the Allergic Responses in a BALB/C Mouse Model of Egg Allergy. Journal of Functional Foods, 67: 103827. Kanouchi, K., Majumder, K., Shibata, H., Mine, Y. (2020). Lactobacillus pentosus S-PT84 and Rubus suavissimus leaf extract suppress lipopolysaccharide-induced gut permeability and egg allergen uptake. Food Production, Processing and Nutrition, 2:4. Majumder, K., Jin, Y., Shibata, H., Mine, Y. (2020). Oral Intervention of Lactobacillus pentosus S-PT84 Attenuates the Allergenic Responses in a BALB/C Mouse Model of Egg Allergy. Molecular Immunology, 120: 43-51. Jacques Izard, Teklu Kuru Gerbaba, and Shara R.P. Yumul. Three-dimensional printing of human microbiome constituents to understand spatial relationships and shape parameters in bacteriology, The American Biology Teacher - In press Shajan Peter, Amanda Pendergraft, William VanDerPol, C. Mel Wilcox, Kondal R Kyanam Kabir Baig, Casey Morrow, Jacques Izard, Peter J. Mannon. Mucosa-associated microbiota in Barrett’s esophagus, dysplasia and esophageal adenocarcinoma differ similarly compared with healthy controls. 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Use of plant proteins as microencapsulating agents of bioactive compounds extracted from annatto seeds (Bixa orellana L.). Antioxidants, 9(4), 310. https://doi.org/10.3390/antiox9040310 Ordoñez‐Quintana, E*., Salmeron, I., Chavez‐Flores, D., Ramos, V., Gutierrez, N., Morales‐Oyervides, L., Delgado, E., Kwofie, E., Ngadi, M., Perez‐Vega, S.B. 2020. Supercritical and subcritical extraction of ursolic acid and polyphenols from apple pomace: Effect of variables on composition and antioxidant capacity. Journal of Food Processing and Preservation, 44(1), e14296. https://doi.org/10.1111/jfpp.14296maize based snacks enriched with grasshopper. International Journal of Food Science & Technology, 53, 1889-1895. DOI:10.1111/ijfs.13774. Melissa M. Melough, Shaowei Wu, Charles Eaton, Abrar A. Qureshi, Ock K. Chun, Eunyoung Cho. Citrus Consumption and Risk of Cutaneous Malignant Melanoma in the Women’s Health Initiative. Nutr Cancer. 2020;72(4):568-575. doi:10.1080/01635581.2019.1644353. Weiyi Sun, Megan S. Rice, Min Kyung Park, Ock K. Chun, Melissa M. Melough, Hongmei Nan, Wenqing Li, Abrar A. Qureshi, Eunyoung Cho. Intake of Furocoumarins and Risk of Skin Cancer in Two Prospective US Cohort Studies. J Nutr. 2020;00:1–10.  <a href="https://doi.org/10.1093/jn/nxaa062">https://doi.org/10.1093/jn/nxaa062</a> Evans R, Engelhorn HJ, Winger QA, Chicco AJ, Bouma GJ. A multiplex PCR genotyping assay to distinguish XX and XY tissues in sheep. Mol Biol Rep in press. PMID:  32743776 Haugen Frenkel JD, Ackart DF, Todd AK, DiLisio JE, Hoffman S, Tanner S, Kiran D, Murray M, Chicco AJ, Obregon-Henao A, Podell B, Basaraba R. Metformin enhances protection in guinea pigs chronically infected with Mycobacterium tuberculosis. Sci Rep in press Le CH, Benage LG, Specht KS, Li Puma LA, Mulligan CM, Heuberger AL, Prenni JE, Claypool SM, Chatfield KC, Sparagna GC, Chicco AJ. Tafazzin deficiency impairs CoA-dependent oxidative metabolism in cardiac mitochondria. 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Impact Statements

W4122 researchers in Illinois have shown that there is a clear effect of thermally-abused frying oil (TAFO) on progression of 4T1 cells injected into the tibia of mice, indicating links between consumption of fried foods using these oils and the development of cancer.

Date of Annual Report: 12/12/2021

Report Information

Annual Meeting Dates: 10/13/2021 - 10/15/2021
Period the Report Covers: 10/10/2020 - 10/15/2021

Participants

See below for the W4122 2021 Annual Meeting minutes, which includes the names, email, and institutional affiliations of all meeting participants listed below:

Pritsos, Cris (pritsos@cabnr.unr.edu) – University of Nevada Reno; Chicco, Adam (adam.chicco@colostate.edu) – Colorado State University; Williams, David (david.williams@oregonstate.edu) – Oregon State University; Delgado, Efren (edelgad@nmsu.edu) – New Mexico State University; Majumder, Kaustav (kasutav.majumder@unl.edu) – University of Nebraska Lincoln; Chen, Chi (chichen@umn.edu) – University of Minnesota; Jacques Izard (jizard@unl.edu)– University of Nebraska; Mohit Verma (msverma@purdue.edu)– Purdue University ; Claudia Maier (claudia.maier@oregonstate.edu)– Oregon State University; Rachel Kopec (kopec.4@osu.edu), Ohio State University; Jay Whelan (jwhelan@utk.edu), Univ of Tennessee.

Brief Summary of Minutes

Minutes Attachment:

W4122 2021 meeting minutes.docx

Accomplishments

Objective 1: Examine the effects of phytochemicals and other dietary components on gut microbiota and intestinal function.  W4122 research in Utah inspired a new USDA seed grant (funded in 2021) to delve further into the dynamics of the gut microbiome response to a wide array of anthocyanin-rich functional foods.  W4122 researchers in Nebraska worked in collaboration with Harvard T.H. Chan School of Public Health on statistical methodology to analyze microbiome data concomitantly with dietary data.  W4122 researchers in Indiana selected a series of thirteen carbohydrates (monosaccharides and disaccharides) that are building blocks of human milk oligosaccharides and used them as a carbon source for the growth of Escherichia coli LF82 and Bacteroides fragilis from the human gut microbiome. After obtaining data on the growth of these bacteria in anaerobic conditions, we observed deterministic behavior based on the type of carbon source used. We developed a new model (based on the logistic growth model) to characterize these complex growth profiles. The introduction of a death term in the model helps quantify and statistically analyze an observed drop in biomass in the data obtained from Bacteroides fragilis. We have also begun testing Ruminococcus species with different nutrient sources as a new collaborative project.  W4122 researchers in Minnesota examined the chemical, physical, and biological properties of processed wheat bran. Health-promoting activities of wheat bran are limited by the high-degree crosslinking of its dietary fiber and the low bioavailability of its phenolics. In this study, functionalized wheat bran (FWB) was prepared through a combination of milling, alkaline hydrolysis, high-shear mixing, and high-pressure homogenization treatments. Feasibility and metabolic effects of feeding FWB were investigated by a short-term mouse feeding trial and the liquid chromatography-mass spectrometry (LC-MS)-based metabolomic analysis. The combinatorial processing dramatically enhanced the function-associated physicochemical properties of wheat bran, including viscosity, fiber compositions, free ferulic acid, and antioxidant capacity. FWB feeding led to diverse positive metabolic effects, including fecal sequestration of bile acids and cholesterol, reduced serum triacylglycerols and cholesterol, elevated fermentation for short-chain fatty acids, increased bioavailability of ferulic acid and its microbial metabolites, and improved redox balance. However, FWB feeding also negatively affected the nutritional status by decreasing the bioavailability of essential amino acids through the excessive loss of amino acids in feces and disrupting lipid homeostasis by reducing choline supply in the liver. These double-edged metabolic effects warrant further investigations on how to achieve the balance between the functionalization of wheat bran bioactives and the disruption of nutrient bioavailability.  W4122 researchers in Colorado are continuing to explore the impact of cricket-derived chitin and other functional foods on the gut microbiota and intestinal function. They simulated the digestive process on ground crickets grown on different substrates and measured total soluble iron content using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). They incubated iron-normalized digests with Caco2 intestinal cells to determine the bioavailability of iron in these samples. Interestingly, the bioavailability of iron was increased when crickets were reared on a substrate consisting of corn stover and mushroom mycelium that had been exposed to fruiting conditions. They are also following up on previous studies showing that 4 weeks of cricket consumption had bifidogenic effects measured in stool samples by specifically isolating cricket chitin and providing a 4g daily dose to individuals with Irritable Bowel Syndrome (IBS) to assess functional gut health and microbiota. The trial is expected to begin in January 2022.  In addition, they established that the anti-obesogenic effects of pulse and dry bean consumption may be due to microbiota modulation. They showed common microbiota signatures across animals consuming different types of pulses and also demonstrated that individual pulses had specific effects on the microbiota- potentially due to different types of fibers.   W4122 researchers in Michigan found that while quercetin and chlorogenic acid did not protect against overt morphological indicators of DSS-induced injury and inflammation or fecal SCFA concentrations, their influence on expression of injury repair molecules, pro-inflammatory cytokines, SCFA transport proteins, and NF-κB inhibitory molecules suggests beneficial influences on major pathways involved in DSS-induced injury/inflammation.  Therefore, in healthy individuals or during periods of remission, quercetin and chlorogenic acid may promote a healthier colon, and may suppress some of the signaling involved in inflammation promotion during active disease.  W4122 researchers in California emphasizes early-life nutrition and development. We use the piglet model to evaluate the effects of micronutrient imbalance (e.g. iron and selecium) and bioactive dietary supplements (e.g. probiotics, synbiotics) on gut health, intestinal microbiome, metabolism, and neurocognitive functions. Despite the impact of COVID on research progress during the reporting period, we have completed 3 research projects wherein we investigated 1) effects of dietary iron levels on risk of enteric bacterial infection, 2) effects of probiotics blends on gut health and microbiome, and 3) the use of prebiotics and synbiotics in modulation of iron absorption and metabolism. Our research is closely related to agriculture and/or human nutrition. Meanwhile, we have customized individual housing units that is equipped with automatic milk delivery system for preweaning piglets. This animal housing and feeding facility allows us to conduct research with milk-fed piglets, a model for formula-fed infants. In the report period, I authored in 9 peer-reviewed papers (corresponding author in 5 of them), submitted 5 proposals as PI or co-PI to NIH, USDA, or industry sponsors, and secured $256,216 funding support. W4122 researchers in Washington:  Inflammatory bowel diseases (IBDs) are chronic and relapsing intestinal inflammation diseases and are associated with dysfunction of the intestinal epithelium. In recent years, metabolic dysregulation has been increasingly implicated in the incidence of IBDs.  Intestinal epithelial cells, positioned between the anaerobic lumen and lamina propria, have a very high metabolic rate. By consuming oxygen, the epithelial layer also controls the anaerobic state of the intestinal lumen, which contributes to microbial homeostasis and dysbiosis. As a natural compound in foods, alpha-ketoglutarate (aKG) is one of the key metabolites maintaining energy homeostasis. As an intermediate of the Krebs cycle, the aKG content in foods varies dramatically, and dietary aKG is a significant source of energy for epithelial cells of the gastrointestinal tract. To test the beneficial effects of dietary aKG against the IBD, we conducted a mouse study using a dextran sulfate sodium (DSS) induced - colitis model. Mice under study received drinking water with or without 1% aKG for four weeks. At week 3, colitis was induced by 2.5% dextran sulfate sodium (DSS) for 7 days followed by 7 days of recovery. We found that dietary aKG supplementation decreased DSS-induced body weight loss, gross bleeding, fecal consistency score, and disease activity index. In agreement, aKG supplementation restored DSS-associated colon shortening, ameliorated mucosal damage, and macrophage infiltration into colonic tissue, which were associated with suppressed gut inflammation and Wnt signaling, improved epithelial structure, enhanced M1 to M2 macrophage polarization, and strengthened intestinal barrier function. Additionally, aKG supplementation elevated colonic aKG levels while decreasing 2-hydroxyglutarate levels, which increased oxidative instead of glycolytic metabolism. In summary, aKG supplementation protects against epithelial damage and ameliorates DSS- induced colitis. Intake of foods enriched with aKG or aKG supplementation can be an alternative approach for the prevention or treatment of colitis that is common in Western societies.   Objective 2: Identify cellular mechanisms and molecular targets of beneficial or adverse dietary components that influence human health.  W4122 researchers in Wisconsin have worked on defining how iron metabolism and red blood cell production is coordinated during postnatal growth is relevant to both production animals and humans.  In swine, iron supplementation during neonatal/postnatal growth is essential to prevent anemia.  Understanding the mechanisms coordination iron metabolism and red cell production may lead to better ways to optimize iron supplementation in swine.  In humans, polycythemia (excess red cell production) can occur throughout the life cycle, from fetal to adult “stages” but the impact on interorgan iron distribution and its potential pathological impacts are not fully understood.  Recent projects have produced data on the impact of IRP1 deficiency in controlling iron metabolism and erythropoiesis.  Similarly, we are collecting data on expression of various mRNAs in renal erythropoietin (Epo) producing cells under a range of conditions.  Epo is the primary hormone driving red blood cell production.  We have submitted a revised version of our manuscript on the regulation of kidney iron metabolism in renal failure.  We anticipate submission of a manuscript on the impact of IRP1 deficiency on systemic iron distribution and heart function in the next few months.  W4122 researchers in New Jersey.  Along the objective of this multi-state project, we examine the potential of dihydromyricetin (DMH) and related metabolites to attenuate acute ethanol-induced impairments. DMH is a natural bioactive flavonoid with unique GABAA receptor activity with a putative mechanism of action to reduce the intoxication effects of ethanol. Although dihydromyricetin's poor oral bioavailability limits clinical utility, the promise of this mechanism for the treatment of alcohol use disorder warrants further investigation into its specificity and druggable potential. These experiments investigated the bioavailability of dihydromyricetin in the brain and serum associated with acute anti-intoxicating effects in C57BL/6J mice. Dihydromyricetin (50 mg/kg IP) administered 0 or 15-min prior to ethanol (PO 5 g/kg) significantly reduced ethanol-induced loss of righting reflex. Total serum exposures (AUC0→24) of dihydromyricetin (PO 50 mg/kg) via oral (PO) administration were determined to be 2.5 µM × h (male) and 0.7 µM × h (female), while intraperitoneal (IP) administration led to 23.8-fold and 7.2- increases in AUC0→24 in male and female mice, respectively. Electrophysiology studies in α5β3γ2 GABAA receptors expressed in Xenopus oocytes suggest dihydromyricetin (10 µM) potentiates GABAergic activity (+43.2%), and the metabolite 4-O-methyl-dihydromyricetin (10 µM) negatively modulates GABAergic activity (-12.6%). Our results indicate that administration route and sex significantly impact DHM bioavailability in mice, which is limited by poor absorption and rapid clearance. This correlates with the observed short duration of DHM's anti-intoxicating properties and highlights the need for further investigation into mechanism of DHM's potential anti-intoxicating properties (Carry et al, 2021).  W4122 researchers in Connecticut determined the relationship between citrus intake and NMSC (skin cancer) risk among postmenopausal women from the Women's Health Initiative (WHI) Observational Study, who were aged 50-79 years at enrollment (1993-1998). The consumption of citrus fruit, citrus juice, and non-citrus fruit and juice were measured at the baseline of the study using a food frequency questionnaire (FFQ). NMSC cases (basal or squamous cell carcinomas) were self-reported during annual follow-up surveys. The outcome data used for this analysis were collected through March 2020. The relative risk (RR) for incident NMSC by citrus consumption was calculated. Among 49,007 non-Hispanic white participants, there were 8642 cases of incident NMSC. Using less than one serving of citrus juice per week as reference, the RRs and 95% confidence intervals (CI) for incident NMSC by citrus juice intake were 1.03 (0.95, 1.10) for one serving/week, 1.06 (1.00, 1.12) for two to four servings/week, 0.98 (0.90, 1.07) for five to six servings/week, and 1.08 (1.02, 1.13) for one or more serving/day (p-trend = 0.007). Subgroup analyses did not reveal meaningful associations by sun exposure variables. W4122 researchers in Colorado investigated the impact of excess dietary fat intake during pregnancy on fetal metabolism and insulin sensitivity using a novel ovine model of fetal metabolic programming. Results indicate that excess fat in the maternal diet promotes a greater capacity of fetal muscle to uptake and oxidize fatty acids, but a reduced capacity for insulin-dependent glucose uptake and oxidation.  This resembles what is seen in obese/insulin-resistant adults, suggesting that the offspring of mothers who consume excess dietary fat during pregnancy may be “programmed” with a greater risk of obesity/diabetes later in life.    W4122 researchers in Colorado investigated the impact of docosahexaenoic acid (DHA) supplementation on fetal metabolism and tissue DHA enrichment using the same ovine model of maternal-fetal metabolic programming. These studies are the first to validate use of an ovine model for investigating the impact of maternal DHA supplementation (MDS) on fetal metabolism and development. Results demonstrate a complex tissue-specific effect of MDS on fetal tissue carbohydrate and fatty acid metabolism that favors a greater capacity for serum glucose disposal and fatty acid oxidation.  Whether these changes ultimately impact nutrient metabolism and cardiometabolic risk in the offspring later in life will be investigated in future studies.  W4122 researchers in Nebraska tested the hypothesis that dietary bioactive peptide (γ-glutamyl peptide: γ-EV) can inhibit inflammation in both vascular tissues to protect against atherosclerosis and associated vascular disorders associated with obesity and inflammation.  To test the biological activity of dietary γ-glutamyl peptide (γ-EV) we have used vascular endothelial cells (HAoEC: Human Aortic Endothelial Cells) in our study. The results obtained from these studies indicated that the intervention of γ-EV can reduce inflammation in vascular endothelial cells by activating the calcium sensing-receptor (CaSR). The results from our absorption study with Caco2 cells indicate that γ-EV can be absorbed. Additional studies revealed that the absorption of γ-EV is via paracellular pathway and Pep-T1 dependent. Additional in-vivo bioavailability study suggests that γ-EV can eb found in the blood stream in a rodent model (SD rats) after an oral gavage of 100mg/kg BW. The peptide has been detected in the blood drawn from the jugular vein as well as in the systemic flow (the blood drawn from the tail snip).  Further in-vivo study with Apolipoprotein E knockout (ApoE-/-) mice showed that intervention of γ-EV both in low dose (50mg/kgBW) and in high dose (250mg/kgBW) can reduce vascular biomarkers like (ICAM-1, VCAM-1, and LOX-1) in the animal model of atherosclerosis.  W4122 researchers in Tennessee, In collaboration with the vascular surgeons of the University of Tennessee Medical Center, Graduate School of Medicine, we started a clinical trial investigating the impact of a combination of dietary bioactives in the stability of peripheral stents. This work was based on a preclinical model of vascular injury (Buckley, M.R., Terry, P.D., Kirkpatrick, S.S., Arnold, J.D., McNally, M.M., Grandas, O.H., Freeman, M.B., Goldman, M.H., Whelan, J., Mountain, D.J.H. 2019. Dietary Supplementation with Zyflamend Poly-Herbal Extracts and Fish Oil Inhibit Intimal Hyperplasia Development Following Vascular Intervention. Nutr Res 68:34-44.) The Clinical Trial has been suspended since March 1, 2020, due to Covid-19, the Delta variant and the low vaccination rates in the state of Tennessee.  W4122 researchers in Oregon, continued collaborative research on Centella asiatica (CA). CA in herbal teas and CA extracts have gained increasing public interest as botanical dietary supplement due to its touted properties to enhance resilience in aging. With our collaborators at OHSU we have developed chemical fingerprinting methods for the characterization of botanical extracts of CA that ensure product integrity of extracts used in preclinical studies.  We further made inroads to confirm a role of caffeoylquinic acids as contributors of bioactivity in the cognitive effects in preclinical rodent models. A vitro study showed minimal induction or inhibition of a range of P450 enzymes, including CYP3A4, by the CA extract, suggesting a low potential for drug interactions modulated by P450 metabolism.  W4122 researchers in Oregon. A number of pharmacokinetics (PK) studies of 3,3’-diindolylmethane (DIM) in both rodents and humans have been published.  No metabolites of DIM have been reported in any of these studies. We were surprised to find robust metabolism of DIM (UPCL-MS/MS) with sulfate (and to some extent glucuronide conjugates) of hydroxylated DIM present in both plasma and urine (Figure 4). In addition to being the first report of DIM metabolites in humans, we demonstrated that one of the hydroxylated metabolites, 2-ox-DIM exhibited pharmacological activity (activation of the aryl hydrocarbon receptor or AHR) greater than the parent phytochemical.   Objective 3: Explore the interaction between dietary components and the host metabolome and epigenome. W4122 researchers in Hawaii. Coffee is the most widely consumed beverage worldwide. Recent studies indicate that drinking moderate amounts of coffee (up to 4 cups/day) may improve mortality rates as well as metabolic abnormalities in humans. Current studies are in progress to identify the effect of Hawaii-grown coffee on plasma metabolome among healthy individuals.   Objective 4: Determine how food processing influences chemical composition to affect human health. W4122 researchers in New Mexico continued their research on glandless cottonseed meal protein oleosin.  Hydrolyzed agro-industrial wastes was used as liquid culture mediums to grow the modified yeast Yarrowia lipolytica to express oleosin from glandless cottonseed protein. We observed that GCSM produces the highest density of yeast at around 20 grams per liter at 96 hours of inoculation. Also, a high number of oil bodies were observed under confocal microscopy after being stained with Red Nile dye compared with the other agro-industrial food wastes. The use of hydrolyzed food waste is an economical and sustainable alternative to be employed as a culture medium and add-value to Agroindustrial byproducts. The proposed technology is also useful on obtaining specific heterologous proteins, single-cell proteins and single-cell oils derived from the yeast. W4122 researchers in Hawaii. Recent studies indicate the beneficial effects of fermentation on food chemical composition and positive influence on human health. We are exploring the role or fermenting bacteria in preparations of traditional Hawaiian medicine noni (Morinda citrifolia) and its effects on obesity and glucose metabolism in mice fed a high-fat diet (manuscript in preparations). We are also investigating the role of bacteria in fermented foods such as sauerkraut and their effects on antioxidant capacity using cell culture models. W4122 researchers in Guam. Collected mango tree leaves (13 varieties) on Guam, extracted mango leaves with methanol and hot water for 24 and 72 hours, and determined anti-diabetic activity of mango leaves (13 varieties) by inhibiting α-amylase assay.   Grants awards (new and ongoing) W4122 members and their labs were awarded over $5.8M in new grants in the 2020-21 period in addition to over $9M in  continuing grant funding to study effects of bioactive nutrients on cancer, diabetes, fetal programming by maternal diet, gut health, and cardiovascular risk). Major awards from this reporting period are listed below. <table width="0"> <tbody> <tr> <td width="237"> Title </td> <td width="128"> Year </td> <td width="132"> Funding Agency </td> <td width="99"> US Dollars (approx.) </td> </tr> <tr> <td width="237"> Training of Next Generation Workforce for Smart Food Science and Agricultural Technology in the Digital Era (WorkFoS-Ag) (Co-PI, $49,258) </td> <td width="128"> 2021 -2024 </td> <td width="132"> USDA-AFRI </td> <td width="99"> 500,000 </td> </tr> <tr> <td width="237"> Transcriptome analysis of Phytophthora blight (Phytophthora capsici) interaction and identifying genes involved in the infection process for early detection of infected plants (PI, 100% of funds). </td> <td width="128"> 2021 - 2023 </td> <td width="132"> NM Chile Association </td> <td width="99"> 91,850 </td> </tr> <tr> <td width="237"> Food Safety: Point-of-Production Chile Screening for Food-Borne Pathogens (Co-PI - 50% of funds) </td> <td width="128"> 2019-2021 </td> <td width="132"> New Mexico Chile Association </td> <td width="99"> 91,281 </td> </tr> <tr> <td width="237"> New Mexico Small Business Assistance Program (PI, 100% of funds) </td> <td width="128"> 2021 </td> <td width="132"> Arrowhead Center, as a contractor for Los Alamos National Laboratory (LANL) </td> <td width="99"> 12,000 </td> </tr> <tr> <td width="237"> ALFA-loT ALliance For Smart Agriculture in the Internet of Things Era (Co-PI – 10 % of funds). </td> <td width="128"> 2018-2022 </td> <td width="132"> USDA- Hispanic Serving Institutions (HSI) </td> <td width="99"> 295,000 </td> </tr> <tr> <td width="237"> Bioprocessing of Agroindustrial By-products (PI–100% of funds) </td> <td width="128"> 2021-2026 </td> <td width="132"> Hatch-Proposal- US Department of Agriculture </td> <td width="99"> 27,500   </td> </tr> <tr> <td width="237"> Food Bioengineering Technology of Agroindustrial Products (PI–100% of funds) </td> <td width="128"> 2016-2021 </td> <td width="132"> Hatch-Proposal- US Department of Agriculture </td> <td width="99"> 27,500   </td> </tr> <tr> <td width="237"> Dynamics of the gut microbiome response to dietary intervention with anthocyanin-rich foods.  Benninghoff (PI).  </td> <td width="128"> 05/21-04/23      </td> <td width="132"> USDA NIFA Grant # 2021-67018-33938 </td> <td width="99">   </td> </tr> <tr> <td width="237"> Field-deployable biosensors for managing animal health </td> <td width="128"> 2021-2023 </td> <td width="132"> Foundation for Food and Agriculture Research </td> <td width="99"> $900,000 </td> </tr> <tr> <td width="237"> International Consortium for Antimicrobial Stewardship in Agriculture Technology Working Group Field-deployable biosensors for antibiotic stewardship </td> <td width="128"> 2021-2022 </td> <td width="132"> Foundation for Food and Agriculture Research </td> <td width="99"> $500,000 </td> </tr> <tr> <td width="237"> Field evaluation of microfluidic paper-based analytical devices for microbial source tracking </td> <td width="128"> 2021-2022 </td> <td width="132"> Center for Produce Safety Grants Program </td> <td width="99"> $390,670 </td> </tr> <tr> <td width="237"> Development of Innovative Technologies and Strategies to Mitigate Biological, Chemical, Physical, and Environmental Threats to Food Safety </td> <td width="128"> 2021-2022 </td> <td width="132"> United States Department of Agriculture Agricultural Research Service </td> <td width="99"> $1,457,128 </td> </tr> <tr> <td width="237"> Smart capsule biosensors </td> <td width="128"> 2021-2022 </td> <td width="132"> Eli Lilly and Company </td> <td width="99"> $98,732 </td> </tr> <tr> <td width="237"> Qualitative and Quantitative analysis of viral particles in continuous processing approach for viral vaccines </td> <td width="128">   </td> <td width="132"> Merck Sharp & Dohme Corp </td> <td width="99"> $75,000 </td> </tr> <tr> <td width="237"> Role of Microbial Dysbiosis and Altered Metabolomics in the Context of Opioid Abuse and ART in HIV Disease Progression </td> <td width="128"> 3/1/17-2/28/22      </td> <td width="132"> NIH 1R01DA043252-01 </td> <td width="99">   </td> </tr> <tr> <td width="237"> Lipocalin 2 as a regulator of phospholipid metabolism in adipose mitochondrial bioenergetics </td> <td width="128"> 1/1/20-12/31/23 </td> <td width="132"> NIH 1R01DK123042-01 </td> <td width="99">   </td> </tr> <tr> <td width="237"> NIH 1R01DK123042-01 </td> <td width="128"> 3/1/2021-12/31/2021 </td> <td width="132"> Sustainable Swine Research </td> <td width="99">   </td> </tr> <tr> <td width="237"> Evaluation of the mechanisms of growth promoting responses of hydroxycinnamic acids (HAC) and their oligomers in weaned pigs </td> <td width="128"> 07/01/2020-06/30/2022 </td> <td width="132"> NSF SSTR program </td> <td width="99">   </td> </tr> <tr> <td width="237"> Beneficial and Adverse Effects of Natural Chemicals on Human Health and Food Safety: Citrus Intake and Skin Cancer Risk </td> <td width="128"> 10/1/2019-9/30/2022 </td> <td width="132"> Hatch Capacity Grant #CONS01012 </td> <td width="99"> $90,000 </td> </tr> <tr> <td width="237"> Attachment Security and the Gut-Brain Axis: A Nationwide Sample </td> <td width="128"> (2021-2022) </td> <td width="132"> ORED Biomedical Research Seed Grant competition </td> <td width="99">   </td> </tr> <tr> <td colspan="4" width="595"> Understanding the Role of the Gastrointestinal Microbiota in Modulating the Antihypertensive Effect of Hydrolysed Egg White. University of Nebraska Collaboration Initiative Grant. $40,000 in total cost, 01/07/2021-30/06/2022 </td> </tr> <tr> <td colspan="4" width="595"> Innovative New Food Uses of Nebraskan Dry-edible Beans. Nebraska Dry Bean Commission. $49,450 in total cost, 01/07/2021-30/06/2022 </td> </tr> <tr> <td colspan="4" width="595"> Nutritional and Functional Enhancement of Yellow Pea for Human Health. University of Nebraska Collaboration Initiative Grant. Santra D (PI), Mitra A (Co-I), Majumder K (Co-I), Pattabiraman M (Co-I). $40,000 in total cost, 01/07/2021-30/06/2022 </td> </tr> <tr> <td colspan="4" width="595"> Elucidating the Health Beneficial Traits of Kernels of Maize Relatives Digested in the Human Gastrointestinal Tract, USDA Agriculture and Food Research Initiative. Priority Area: A1141 Plant Breeding for Agricultural Production. Project No: NEB-30-135. Obata T (PI), Majumder K (Co-I), Yang J (Co-I). $500,000 in total cost, 01/15/2021-01/14/2024 </td> </tr> <tr> <td colspan="4" width="595"> U19 AT010829 - Botanical Dietary Supplement Center (BDSRC). (PI: Amala Soumyanath, OHSU)  07/01/2020 - 06/30/2025, NIH/NCCIH. Botanicals enhancing neurological and functional resilience in aging (BENFRA), $414,243 (Annual DC). Total $1,5 Mio (for OSU). (TOTAL ALL COMPONENTS: $6.0 Mio) </td> </tr> <tr> <td colspan="4" width="595"> R01 AT010271. (Multi-PIs: Stevens (contact), Bradley, Metz)        01/01/19-12/31/22 NIH/NCCIH. Discovery and Biological Signatures of Microbiome-Derived Xanthohumol Metabolites and their Role in Ameliorating Inflammatory Bowel Disease. $345,786 (Annual DC) </td> </tr> <tr> <td colspan="4" width="595"> S10 OD026922 (PI: Maier)     02/01/2019-08/31/2021. NIH Office of the Director. Ultra-Performance Liquid Chromatography Tandem Quadrupole Mass Spectrometry System. This project requests funds for the purchase of a tandem quadruple LC-MS platform to support 8 major NIH-funded user projects and multiple smaller user projects with needs in accurate quantifications of small molecules, peptides and proteins. Role: PI. $577,208 </td> </tr> <tr> <td colspan="4" width="595"> USDA.  Co-PI with Kelly Millenbah, Darrell Donahue, and Randy Showerman.  Food processing, technology, and safety workforce development:  Dual certificate and associate degree program.  9/1/20-8/31/25.  Funded $367,646.36 direct/$499,999.08 total costs. </td> </tr> <tr> <td colspan="4" width="595"> California Prune Board.  PI.  Colon cancer protection derived from prunes.  $26,000 direct/total costs for a 1 year project.  10/1/21 – 9/30/22.  Funded $26,000 direct/total costs. </td> </tr> <tr> <td colspan="4" width="595"> 2020-09321 (Nerurkar, PI)                                                                 04/01/21 – 03/31/26 AFRI-NIFA REEU (competitive grants)                    Direct - $440,367; indirect – $59,633. Empowering Women and Underrepresented Undergraduates with Advanced Technology Research Training in Agriculture and Food Sciences </td> </tr> <tr> <td colspan="4" width="595"> 5604322 (Nerurkar, PI)                                                                      07/01/21 – 06/30/22 CTAHR Internal Funds, $32,606. Seed funding application to retain MS student and generate preliminary data. Project investigates the role of bacteria to modulate antioxidant activities of fermented foods. </td> </tr> <tr> <td colspan="4" width="595"> USDA/Colorado AES (Chicco, PI)    $50,000                                   07/01/21 – 06/30/23 Tissue-specific role of FADS2 in dietary regulation of cardiometabolic risk. Project investigates the role of dietary essential polyunsaturated fatty acid metabolism by FADS2 on cardiometabolic heath parameters in muring models. </td> </tr> <tr> <td colspan="4" width="595"> 00000 (Ho K.),   2021 Equipment Grant for LM20 Microfluidizer High Shear Fluid Processor.                  $37567 </td> </tr> <tr> <td colspan="4" width="595"> Probiotics and gut health and development. (Sponsor: DuPont) </td> </tr> <tr> <td colspan="4" width="595"> Use of feed enzyme to enhances resistance to enterotoxigenic E. coli infection in pigs. (Sponsor: DuPont) </td> </tr> <tr> <td colspan="4" width="595"> Zhu, M. J. (PI), Navarre, R., Chew, B. USDA-NIFA (2018-67017-27517). Pigmented potato restores gut epithelial health impaired by obesity. $500,000 (5/2018 – 5/2022) </td> </tr> <tr> <td colspan="4" width="595"> Du, M., Zhu, M. J. (co-PI). NIH (R01HD067449). Maternal obesity, AMPK and fetal brown adipogenesis. $ 1,561,745 (8/2017-7/2022).   1R21HD097601-01 (NIH/NICHD) “Integrative metabolism of oocyte development and its modulation by maternal diet”  (Chicco, PI) 9/2018- 9/2021;  $401,909 </td> </tr> </tbody> </table>

Publications

There were 86 new publications by W4122 members in 2020-2021 reporting period, addressing the effects of bioactive nutrients on health and chronic disease risk, basic insights into nutrient metabolism, and the development of new methodology and technologies for studying these processes in humans and model systems.  Publications are listed below with W4122 group members in boldfaced text. <ol> <li>Trikha SRJ, Lee DM, Ecton KA, Wrigley SD, Vazquez AR, Litwin NS, Thomas KN, Battson ML, Johnson SA, Kuhn KA, Colgan SP, Gentile CG, Weir TL (2021) Vascular Dysfunction and Glucose Intolerance are Transferrable to Germ Free Mice via an Obesity-Associated Human Microbiota. Gut Microbes 13(1): 1940791. IF: 10.245</li> <li>Freedman KE, Hill JL, Wei Y, Vazquez AR, Grubb DS, Trotter RE, Wrigley SD, Johnson SA, Foster MT, Weir TL (2021) Examining the immunomodulatory effects of novel probiotic Bacillus subtilis DE111. J. Mol. Sci. 22, 2453. https://doi.org/10.3390/ijms22052453 IF: 5.923</li> <li>Williams NNB, Ewell TR, Abbotts KSS, Harms KJ, Woelfel KA, Dooley GP, Weir TL, Bell C (2021) Comparison of five oral cannabidiol preparations in adult humans: Pharmacokinetics, body composition, and heart rate variability. Pharmaceuticals 14, 35. doi: 10.3390/ph14010035. IF: 6.321</li> <li>Johnson SA, Prenni J, Heuberger AL, Isweiri H, Chaparro J, Newman S, Uchanski M, Omerigic H, Michell K, Bunning M, Foster MT, Thompson HJ, Weir TL (2020) Comprehensive Evaluation of Metabolites and Minerals in Six Microgreen Species and the Influence of Maturity. Curr Dev Nutr nzaa180, doi: 10.1093/cdn/nzaa180</li> <li>Soderborg TK, Carpenter C, Janssen RC, Weir TL, Young BE, Krebs NF, Hernandez TL, Barbour LA, Frank DN, Kroehl M, Friedman JE. (2020) Gestational diabetes is uniquely associated with altered early seeding of the infant gut microbiota. Front Endocrinol doi:10.3389/fendo.2020.603021 IF: 3.675</li> <li>Grubb DS, Wrigley SD, Freedman KE, Wei Y, Vazquez AR, Trotter RE, Wallace TC, Johnson SA and Weir TL (2020) PHAGE-2 Study: Supplemental Bacteriophages Extend Bifidobacterium animalis subsp. lactis BL04 Benefits on Gut Health and Microbiota. Nutrients 12, 2474; doi.org/10.3390/nu12082474 IF:5.717</li> <li>Weir TL, Trikha SRJ, Thompson HJ (2020) Diet and Risk of Cancer Reduction: The Role of Diet-Microbiota Interactions and Microbial Metabolites. Seminars in Cancer Biology DOI: 10.1016/ j.semcancer.2020.06.007 IF:15.707</li> <li>Trotter RE, Vazquez AR, Grubb DS, Freedman KE, Wei Y, Jones S, Gentile CL, Melby CL, Johnson SA, Weir TL (2020) Examining the Impact of Probiotic Supplement Intake on Endothelial Function and Lipid Metabolism in Healthy Adults. Beneficial Microbes 11 (7): 621-630. IF: 4.205</li> <li>Lee DM, Ecton KE, Trikha SRJ, Wrigley SD, Thomas KN, Battson ML, Wei Y, Johnson SA, Weir TL, and Gentile CL (2020) Microbial Metabolite Indole-3-Propionic Acid Supplementation Does Not Protect Mice from the Cardiometabolic Consequences of a Western Diet. Am J Physiol-Gastro Liver Physiolorg/10.1152/ajpgi.00375.2019 IF: 4.052</li> <li>Bermúdez-Quiñones, G., Ochoa-Martinez, A., Gallegos-Infante, J.A., Rutiaga-Quiñones, O.M., Lara-Ceniceros T., Delgado, E., Gonzalez-Herrea, S.M. 2021. Synbiotic microcapsules using agavins and inulin as wall materials for Lactobacillus casei and Bifidobacterium breve: Viability, physicochemical properties, and resistance to in vitro oro-gastrointestinal transit. Journal of Food Processing and Preservation. Accepted for publication October,</li> <li>Delgado E., Valles-Rosales D. J., Pámanes-Carrasco G. A., Cooke P., Flores N. C., Reyes-Jáquez D. 2021. Structural, rheological, and calorimetric properties of an extruded shrimp feed using glandless cottonseed meal as a protein source. Journal of Aquaculture Research and Development 12(3), 627. Impact factor 1.27.</li> <li>Delgado, E., Alvarado-González*, Ó., Medrano-Roldán, H., Rodríguez-Miranda, J., Carrete-Carreón, F., Reyes-Jáquez, D. 2021. Evaluation of fish oil content and cottonseed meal with ultralow gossypol content on the functional properties of an extruded shrimp feed. Aquaculture Reports 19, 1-6. https://doi.org/10.1016/j.aqrep.2021.100588. Impact factor 2.289.</li> <li>Velazquez-Martinez, V., Valles-Rosales, D., Rodriguez-Uribe, L., Holguin, O., Quintero-Quiroz, J., Reyes-Jaquez, D., Rodriguez-Borbon, M.I., Villagrán-Villegas, L.Y., Delgado, E. 2021. Antimicrobial, shelf-life stability, and effect of maltodextrin and gum arabic on the encapsulation efficiency of sugarcane bagasse bioactive compounds. Foods 10(1), 115, https://doi.org/10.3390/foods10010116. Impact factor: 4.092.</li> <li>Whelan, J., 2021. Allometric scaling of dietary bioactives in metabolic research: The Present and Future. In: Nutritional Signaling Pathway Activities. In the series: Obesity and Diabetes Food Chemistry, Function and Analysis No. 24, Ed: Zhiyong Cheng, Royal Society of Chemistry, Chapter 11, Pp. 295-309.</li> <li>Aardema, N.D, Rodriguez, D.M, Van Wettere, A., Benninghoff, A., Hintze, K.J, (2021). The Western Dietary Pattern Combined with Vancomycin-Mediated Changes to the Gut Microbiome Exacerbates Colitis Severity and Colon Tumorigenesis. Nutrients, 13:3, 881. doi: 10.3390/nu13030881</li> <li>Chauhan, S, Wagner, J.G, Benninghoff, A., Lewandowski, R.P, Favor, O.K, Wierenga, K.A, Gilley, K.N, Ross, E.A, Harakema, J.R, Pestka, J.J, (2021). Rapid Induction of Pulmonary Inflammation, Autoimmune Gene Expression, and Ectopic Lymphoid Neogenesis Following Acute Silica Exposure in Lupus-Prone Mice. Frontiers in Immunology, 12, 635138. doi: 10.3389/fimmu.2021.635138</li> <li>Rajasinghe, L.D, Li, Q.Z, Zhu, C., Yan, M., Chauhan, P.S, Wierenga, K.A, Bates, M.A, Harkema, J.R, Benninghoff, A., Pestka, J.J, (2020). Omega-3 fatty acid intake suppresses induction of diverse autoantibody repertoire by crystalline silica in lupus-prone mice. Autoimmunity, 53:7, 415-433. doi: 10.1080/08916934.2020.1801651</li> <li>Wierenga, K.A, Strakovsky, R.S, Benninghoff, A., Rajasinghe, L.D, Lock, A.L, Harkema, J.R, Pestka, J.J, (2020). Requisite Omega-3 HUFA Biomarker Thresholds for Preventing Murine Lupus Flaring. Frontiers in Immunology, 11, 1796. doi: 10.3389/fimmu.2020.01796</li> <li>Gilley, K.N, Wierenga, K.A, Chauhuan, P.S, Wagner, J.G, Lewandowski, R.P, Ross, E.A, Lock, A.L, Harkema, J.R, Benninghoff, A., Pestka, J.J, (2020). Influence of total western diet on docosahexaenoic acid suppression of silica-triggered lupus flaring in NZBWF1 mice. Plos One, 15:5, e0233183. doi: 10.1371/journal.pone.0233183</li> <li>Benninghoff, A., Hintze, K.J, Monsanto, S., Rodriguez, D.M, Hunter, A., Phatak, S., Pestka, J.J, Van Wettere, A., Ward, R.E, (2020). Consumption of the total Western diet promotes colitis and inflammation-associated colorectal cancer in mice. Nutrients, 12:2, 544. doi: 10.3390/nu12020544</li> <li>Pascual-Garrigos, A., Maruthamuthu, M.K., Ault, A., Davidson, J., Rudakov, G., Pillai, D., Koziol, J., Schoonmaker, J., Johnson, T., Verma, M.S.* (Accepted: 3 September, 2021) On-farm colorimetric detection of Pasteurella multocida, Mannheimia haemolytica, and Histophilus somni in crude bovine nasal samples. Veterinary Research</li> <li>Davidson, J.L., § Wang, J.W., § Maruthamuthu, M.K.,§ Dextre, A., Pascual-Garrigos, A., Mohan, S., Putikam, S.V.S., Osman, F.O.I., McChesney, D., Seville, J., Verma, M.S.* (2021) A paper-based colorimetric molecular test for SARS-CoV-2 in saliva. Biosensors and Bioelectronics: X; 9: 100076. DOI: 10.1016/j.biosx.2021.100076</li> <li>Mohan, S.,§ Pascual-Garrigos, A.,§ Brouwer, H., Pillai, D., Koziol, J., Ault, A., Schoonmaker, J., Johnson, T., Verma, M.S.* (2021) Loop-mediated isothermal amplification for the detection of Pasteurella multocida, Mannheimia haemolytica, and Histophilus somni in bovine nasal samples. ACS Agricultural Science and Technology; 1: 100-108. DOI:10.1021/acsagscitech.0c00072</li> <li>Ma Y, Lu Y, Petrofsky K, Liu J, Cheng Y, Ruan R, Chen Double-edged metabolic effects from a short-term feeding of functionalized wheat bran in mouse revealed by metabolomic profiling. J Agric Food Chem. 69: 6543-6555 (2021)</li> <li>Peng L, Yuan J, Yao D, Chen Fingerprinting triacylglycerols and aldehydes as identity and thermal stability indicators of camellia oil through chemometric comparison with olive oil. Food Science and Nutrition. 9: 2561–2575 (2021)</li> <li>Mao Q, Liu J, Wiertzema JR, Chen D, Chen P, Baumler DJ, Ruan R, Chen Identification of Quinone Degradation as a Triggering Event for Intense Pulsed Light-Elicited Metabolic Changes in Escherichia coli by Metabolomic Fingerprinting. Metabolites. 11:102 (2021)</li> <li>Cui W, Sathyanarayan A, Lopresti M, Aghajan M, Chen C, Mashek DG. Lipophagy-derived fatty acids undergo extracellular efflux via lysosomal exocytosis. Autophagy 17, 690-705 (2021)</li> <li>Zhu XH, Lee BY, Tuite P, Coles L, Sathe AG, Chen C, Cloyd J, Low WC, Steer CJ, Chen W. Quantitative Assessment of Occipital Metabolic and Energetic Changes in Parkinson’s Patients, Using In Vivo 31P MRS-Based Metabolic Imaging at 7T. Metabolites. 11:145 (2021)</li> <li>Qiu X, Macchietto MG, Liu X, Lu Y, Ma Y, Guo H, Saqui-Salces M, Bernlohr DA, Chen C, Shen S, Chen X. Identification of gut microbiota and microbial metabolites regulated by an antimicrobial peptide lipocalin 2 in high fat diet-induced obesity. Int J Obes (Lond). 45:143-154 (2021)</li> <li>Chen D, Mosher W, Wiertzema J, Peng P, Min M, Cheng Y, An J, Ma Y, Fan X, Niemira BA, Baumler DJ, Chen C, Chen P, Ruan R. Effects of intense pulsed light and gamma irradiation on Bacillus cereus spores in mesquite pod flour. Food Chem. 344:128675 (2021)</li> <li>Fritsch J, Garces L, Quintero MA, Pignac-Kobinger J, Santander AM, Fernández I, Ban YJ, Kwon D, Phillips MC, Knight K, Mao Q, Santaolalla R, Chen XS, Maruthamuthu M, Solis N, Damas OM, Kerman DH, Deshpande AR, Lewis JE, Chen C, Abreu MT, Low-fat, High-fiber Diet Reduces Markers of Inflammation and Dysbiosis and Improves Quality of Life in Patients With Ulcerative Colitis. Clin Gastroenterol Hepatol. 19: 1189-1199 (2021)</li> <li>Junichi R. Sakaki, Melissa M. Melough, Mary B. Roberts, Charles B. Eaton, Aladdin H. Shadyab, Abrar A. Qureshi, Ock K. Chun and Eunyoung Cho§. Citrus Consumption and Risk of Non-melanoma Skin Cancer in the Women’s Health Initiative. Cancers 2021, 13(9), 2173; https://doi.org/10.3390/cancers13092173. §Co-corresponding authors</li> <li>Melissa M. Melough, Shaowei Wu, Charles Eaton, Abrar A. Qureshi, Ock K. Chun, Eunyoung Cho§. Citrus Consumption and Risk of Cutaneous Malignant Melanoma in the Women’s Health Initiative. Nutr Cancer. 2020;72(4):568-575. doi:10.1080/01635581.2019.1644353.</li> <li>Co-corresponding authors</li> <li>Weiyi Sun, Megan S. Rice, Min Kyung Park, Ock K. Chun, Melissa M. Melough, Hongmei Nan, Wenqing Li, Abrar A. Qureshi, Eunyoung Cho. Intake of Furocoumarins and Risk of Skin Cancer in Two Prospective US Cohort Studies. J Nutr. 2020;00:1–10. <a href="https://doi.org/10.1093/jn/nxaa062">https://doi.org/10.1093/jn/nxaa062</a>.</li> <li>Long H. Nguyen*, Yin Cao*, Jinhee Hur, Raaj S. Mehta, Daniel R. Sikavi, Yiqing Wang, Wenjie Ma, Kana Wu, Mingyang Song, Edward L. Giovannucci, Eric B. Rimm, Walter C. Willett, Wendy S. Garrett, Jacques Izard, Curtis Huttenhower*, Andrew T. Chan*. The sulfur microbial diet is associated with risk of early-onset colorectal cancer precursors. Gastroenterology – In Press.</li> <li>Lisa A. Whisenhunt, Linda H. Xu*, Fan Yang*, and Jacques Izard. Output Consistency Scale to Standardize Ostomate Output Description in Clinical Practice and Studies. Academic Journal of Gastroenterology & Hepatology (2021) vol. 3(1) AJGH.MS.ID.000554</li> <li>Daniel R. Sikavi, Long H. Nguyen, Koichiro Haruki, Tomotaka Ugai, Wenjie Ma, Dong D. Wang, Kelsey Thompson, Yan Yan, Tobyn Branck, Jeremy Wilkinson, Naohiko Akimoto, Rong Zhong, Mai Chan Lau, Kosuke Mima, Keisuke Kosumi, Teppei Morikawa, Eric B. Rimm, Wendy S. Garrett, Jacques Izard, Yin Cao, Mingyang Song, Curtis Huttenhower, Shuji Ogino and Andrew T. Chan. The sulfur microbial diet and risk of colorectal cancer by molecular subtypes and intratumoral microbial species in adult men. Clinical and Translational Gastroenterology (2021), Vol. 12(8) p. e00338.</li> <li>Wenjie Ma, Long H. Nguyen, Mingyang Song, Daniel D. Wang, Eric Franzosa, Yin Cao, Amit Joshi, David A. Drew, Raaj Mehta, Kerry L. Ivey, Lisa L. Strate, Edward L. Giovannucci, Jacques Izard, Wendy Garrett, Eric B. Rimm, Curtis Huttenhower, and Andrew T. Chan. Dietary fiber intake, the gut microbiome, and chronic systemic inflammation in a cohort of adult men. Genome Medicine (2021), vol. 13, article 102.</li> <li>Christine Everett, Chengchen Li, Jeremy E. Wilkinson, Long Nguyen, Lauren McIver, Kerry Ivey, Jacques Izard, Natalia Palacios, A. Heather Eliassen, Walter C. Willett, Alberto Ascherio, Qi Sun, Shelley S. Tworoger, Andrew T. Chan, Wendy S. Garrett, Curtis Huttenhower, Eric B. Rimm, and Mingyang Song. Overview of the microbiome among Nurses study (Micro-N) as an example of prospective characterization of the microbiome within cohort studies. Nature Protocols (2021), Vol. 16, p. 2724-2731 (DOI: 10.1038/s41596-021-00519-z).</li> <li>Jacques Izard, Teklu Kuru Gerbaba, and Shara R.P. Yumul. Three-dimensional printing of human microbiome constituents to understand spatial relationships and shape parameters in bacteriology. The American Biology Teacher (2021), vol. 83 (3), p. 188-190.</li> <li>Mei Chung, Naisi Zhao, Richard Meier, Devin C. Koestler, Guojun Wu, Erika Del Castillo, Bruce J. Paster, Kevin Charpentier, Jacques Izard, Karl T. Kelsey, and Dominique S. Comparisons of oral, intestinal, and pancreatic bacterial microbiomes in patients with pancreatic cancer and other gastrointestinal diseases. Michaud Journal of Oral Microbiology (2021), vol. 83 (13) 1887680.</li> <li>Guha S^, Alvarez S, Mine Y, Majumder K*. (2021). Transport of Dietary Anti-Inflammatory Peptide, γ-Glutamyl Valine (γ-EV), across the Intestinal Caco-2 Monolayer. Nutrients, 13, 1448. doi: 10.3390/nu13051448.</li> <li>Nolasco E^, Yang J, Ciftci O, Vu CD, Alvarez S, Purdum, S, Majumder K*. (2021). Evaluating the Effect of Cooking and Gastrointestinal Digestion in Modulating the Bio-accessibility of Different Bioactive Compounds of Eggs. Food Chemistry, 344, 128623. doi: 10.1016/j.foodchem.2020.128623.</li> <li>Matthews DG, Caruso M, Alcazar Magana A, Wright KM, Maier CS, Stevens JF, Gray NE, Quinn JF, Soumyanath A. Caffeoylquinic Acids in Centella asiatica Reverse Cognitive Deficits in Male 5XFAD Alzheimer's Disease Model Mice. Nutrients. 2020 Nov 13;12(11):3488. doi: 10.3390/nu12113488. PMID: 33202902</li> <li>Paraiso IL, Tran TQ, Magana AA, Kundu P, Choi J, Maier CS, Bobe G, Raber J, Kioussi C, Stevens JF. Xanthohumol ameliorates Diet-Induced Liver Dysfunction via Farnesoid X Receptor-Dependent and Independent Signaling. Front Pharmacol. 2021 Apr 20;12:643857. doi: 10.3389/fphar.2021.643857. eCollection 2021. PMID: 33959012</li> <li>Zhang Y, Bobe G, Miranda CL, Lowry MB, Hsu VL, Lohr CV, Wong CP, Jump DB, Robinson MM, Sharpton TJ, Maier CS, Stevens JF, Gombart AF. Tetrahydroxanthohumol, a xanthohumol derivative, attenuates high-fat diet-induced hepatic steatosis by antagonizing PPARγ. Elife. 2021 Jun 15;10:e66398. doi: 10.7554/eLife.66398. PMID: 34128467</li> <li>Alcázar Magaña A, Kamimura N, Soumyanath A, Stevens JF, Maier Caffeoylquinic acids: chemistry, biosynthesis, occurrence, analytical challenges, and bioactivity. Plant J. 2021 Sep;107(5):1299-1319. doi: 10.1111/tpj.15390. Epub 2021 Jul 23. PMID: 34171156 Review.</li> <li>Logan IE, Shulzhenko N, Sharpton TJ, Bobe G, Liu K, Nuss S, Jones ML, Miranda CL, Vasquez-Perez S, Pennington JM, Leonard SW, Choi J, Wu W, Gurung M, Kim JP, Lowry MB, Morgun A, Maier CS, Stevens JF, Gombart AF. Xanthohumol Requires the Intestinal Microbiota to Improve Glucose Metabolism in Diet-Induced Obese Mice. Mol Nutr Food Res. 2021 Sep 8:e2100389. doi: 10.1002/mnfr.202100389. Online ahead of print. PMID: 34496124.</li> <li>Yap ESP, Uthairatanakij A, Laohakunjit N, Jitareerat P, Vaswani A, Magana AA, Morre J, Maier Plant growth and metabolic changes in 'Super Hot' chili fruit (Capsicum annuum) exposed to supplemental LED lights. Plant Sci. 2021 Apr;305:110826. doi: 10.1016/j.plantsci.2021.110826. Epub 2021 Jan 14. PMID: 33691960</li> <li>Weinman MA, Ramsey SA, Leeper HJ, Brady JV, Schlueter A, Stanisheuski S, Maier CS, Miller T, Ruby CE, Bracha S. Exosomal proteomic signatures correlate with drug resistance and carboplatin treatment outcome in a spontaneous model of canine osteosarcoma. Cancer Cell Int. 2021 May 1;21(1):245. doi: 10.1186/s12935-021-01943-7.PMID: 33933069</li> <li>Le DE, García-Jaramillo M, Bobe G, Alcazar Magana A, Vaswani A, Minnier J, Jump DB, Rinkevich D, Alkayed NJ, Maier CS, Kaul S. Plasma Oxylipins: A Potential Risk Assessment Tool in Atherosclerotic Coronary Artery Disease. Front Cardiovasc Med. 2021 Apr 21;8:645786. doi: 10.3389/fcvm.2021.645786. eCollection 2021. PMID: 33969011</li> <li>Vaswani A, Alcazar Magana A, Zimmermann E, Hasan W, Raman J, Maier Comparative liquid chromatography/tandem mass spectrometry lipidomics analysis of macaque heart tissue flash-frozen or embedded in optimal cutting temperature polymer (OCT): Practical considerations. Rapid Commun Mass Spectrom. 2021 Sep 30;35(18):e9155. doi: 10.1002/rcm.9155. PMID: 34169582</li> <li>Park S, Maier CS, Koley D. Anodic Stripping Voltammetry on a Carbon-based Ion-Selective Electrode. Electrochim Acta. 2021 Sep 10;390:138855. doi: 10.1016/j.electacta.2021.138855. Epub 2021 Jul 2. PMID: 34483347.</li> <li>Little-Letsinger, S.E., N.D. Turner, J.R. Ford, L.J. Suva, and S.A. Bloomfield.   Omega-3 fatty acid modulation of serum and osteocyte tumor necrosis factor-a in adult mice exposed to ionizing radiation.  Journal of Applied Physiology (1985) 130:627-639.</li> <li>Turner, N.D. and J.R. Lupton.   Dietary fiber.  Advances in Nutrition.  (Accepted 9/7/21).</li> <li>Nerurkar PV*, Gandhi, K and Chen JJ. Correlations between coffee consumption and metabolic phenotypes, plasma folate, and vitamin B12: NHANES 2003 to 2006. Nutrients, 2021, 13 (4), 1348 -1366. <a href="https://www.mdpi.com/2072-6643/13/4/1348">https://www.mdpi.com/2072-6643/13/4/1348</a>.</li> <li>Williams, D.E. (2021) Indoles Derived From Glucobrassicin: Cancer Chemoprevention by Indole-3-Carbinol and 3,3'-Diindolylmethane. Front. 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Development and validation of a micro-QuEChERS method with high-throughput enhanced matrix removal followed with UHPLC-QqQ-MS/MS for analysis of raspberry ketone-related phenolic compounds in adipose tissues. Talanta. 2021 Dec 1;235:122716. doi: 10.1016/j.talanta.2021.122716. Epub 2021 Jul 13. PMID: 34517584; PMCID: PMC8441007.</li> <li>Lee JJ, Kim S, Cho JH, Kyoung H, Lee S, Choe J, Liu Y, Ji P, Xiong X, Kim Y, Kim HB. Potential use of ground brown rice for weanling pigs. Journal of Animal Science. 2021 Oct;99(10):skab267.</li> <li>Qi M, Tan B, Wang J, Liao S, Li J, Cui Z, Shao Y, Ji P, Yin Y. Postnatal growth retardation is associated with deteriorated intestinal mucosal barrier function using a porcine model. Journal of Cellular Physiology. 2021 Apr;236(4):2631-48.</li> <li>He Y, Liu Y, Ji Metabolomic Profile of Weaned Pigs Challenged with E. coli and Supplemented with Carbadox or Bacillus subtilis. Metabolites. 2021 Feb;11(2):81.</li> <li>Qi M, Tan B, Wang J, Liao S, Deng Y, Ji P, Song T, Zha A, Yin Y. The microbiota–gut–brain axis: A novel nutritional therapeutic target for growth retardation. Critical Reviews in Food Science and Nutrition. 2021 Jan 25:1-26.</li> <li>Kim K, Kim B, Kyoung H, Liu Y, Campbell J, Song M, Ji P. Dietary spray-dried plasma supplementation in late-gestation and lactation enhanced productive performance and immune responses of lactating sows and their litters. Journal of Animal Science and Technology. 2021.</li> <li>Perng V, Li C, Klocke CR, Navazesh SE, Pinneles DK, Lein PJ, Ji P. Iron Deficiency and Iron Excess Differently Affect Dendritic Architecture of Pyramidal Neurons in the Hippocampus of Piglets. The Journal of nutrition. 2021 Jan;151(1):235-44.</li> <li>Kim K, Ji P, Song M, Che TM, Bravo D, Pettigrew JE, Liu Y. Dietary plant extracts modulate gene expression profiles in alveolar macrophages of pigs experimentally infected with porcine reproductive and respiratory syndrome virus. Journal of animal science and biotechnology. 2020 Dec;11(1):1-4.</li> <li>Doan N, Liu Y, Xiong X, Kim K, Wu Z, Bravo DM, Blanchard A, Ji P. Organic selenium supplement partially alleviated diquat-induced oxidative insults and hepatic metabolic stress in nursery pigs. British Journal of Nutrition. 2020 Jul;124(1):23-33.</li> <li>Bravo Iniguez, A., and M. J. Zhu. 2021. Hop bioactive compounds in prevention of nutrition-related noncommunicable diseases. Critical Reviews in Food Science and Nutrition, 61: 1900-1913.</li> <li>Chen, Y., G. Ma, Y. Hu, Q. Yang, J. M. Deavila, M. J. Zhu, and M. Du. 2021. Effects of maternal exercise during pregnancy on perinatal growth and childhood obesity outcomes: a meta-analysis and meta-regression. Sports Medicine, 51: 2329-2347.</li> <li>Chen, Y. T., Y. Hu, Q. Y. Yang, X. D. Liu, J. S. 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Excessive glucocorticoids during pregnancy impair fetal brown fat development and predisposes offspring to metabolic dysfunctions. Diabetes, 69:1662-1674.</li> <li>Son, J. S., L. Zhao, Y. Chen, K. Chen, S. A. Chae, J. M. de Avila, H. Wang, M.J. Zhu, Z. Jiang and M. Du. 2020. Maternal exercise via exerkine apelin enhances brown adipogenesis and prevents metabolic dysfunction in offspring mice. Science Advances, 6: eaaz0359.</li> <li>Son, J. S., S. A. Chae, H. Wang, Y. Chen, A. B. Iniguez, J. M. de Avila, M. J. Zhu, and M. Du. 2020. Maternal inactivity programs skeletal muscle dysfunction in offspring mice via attenuating apelin signaling and mitochondrial biogenesis. Cell Report, 33: 108461.</li> <li>Tian, Q., J. Zhao, Q. Yang, B. Wang, J. Deavila, M. J. Zhu, and M. Du. 2020. Dietary alpha-ketoglutarate promotes beige adipogenesis and prevents obesity in middle-aged mice. Aging Cell, 19: e13059.</li> <li>Tian, Q., Z. Xu, X. Sun, J. Deavila, M. Du, and M. J. Zhu. 2020. Grape pomace inhibits colon carcinogenesis by suppressing cell proliferation and inducing epigenetic modifications. Journal of Nutritional Biochemistry, 84:108443.</li> <li>Chatfield KC, Sparagna GC, Specht KS, Whitcomb L, Omar A, Wolfe LA, Chicco Long-chain fatty acid oxidation and respiratory complex I deficiencies distinguish Barth Syndrome from idiopathic pediatric cardiomyopathy – In press, J Inher Metab Dis</li> <li>Wallace T, Schaeuble D, Pace SA, Schackmuth MK, Hentges ST, Chicco AJ, Myers B. Sexually divergent cortical control of affective-autonomic integration. Psychoneuroendocrinology in press</li> <li>Catandi GD, Obeidat Y, Broeckling CD, Chen T, Chicco AJ, Carnevale EM. Equine maternal aging affects oocyte lipid content, metabolic function and developmental potential. Reproduction, 161(4):399-409, 2021. PMID: 33539317</li> </ol>

Impact Statements

All the aforementioned W4122 research activities provided training opportunities for graduate students, undergraduate, postdoc, and/or visiting scholars.