W5122: Beneficial and Adverse Effects of Natural Chemicals on Human Health and Food Safety

(Multistate Research Project)

Status: Active

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SAES-422 Reports

Annual/Termination Reports:

[02/15/2023] [02/15/2024] [03/14/2025]

Date of Annual Report: 02/15/2023

Report Information

Annual Meeting Dates: 10/13/2022 - 10/14/2022
Period the Report Covers: 10/01/2021 - 09/30/2022

Participants

See Attached Minutes of meeting

Participants Attachment:

W5122 Multistate Research Activity 2022 Accomplishments Report_2022.docx

Brief Summary of Minutes

See attached minutes

Accomplishments

See attached minutes

Publications

See attached minutes

Impact Statements

See meeting minutes

Date of Annual Report: 02/15/2024

Report Information

Annual Meeting Dates: 10/12/2023 - 10/13/2023
Period the Report Covers: 10/14/2022 - 10/12/2023

Participants

• Nancy Turner (ndturner@msu.edu) - Michigan State University
• Hongbing Fan (Hongbing.Fan@uky.edu) - University of Kentucky
• Tiffany Weir (tiffany.weir@colostate.edu) - Colorado State University
• Efren Delgado (edelgad@nmsu.edu) - New Mexico State University
• Bill Helferich (helferic@illinois.edu) - University of Illinois
• Chi Chen (chichen@umn.edu) - University of Minnesota
• Kaustav Majumder (kaustav.majumder@unl.edu) – University of Nebraska-Lincoln
• Adam Chicco (adam.chicco@colostate.edu) - Colorado State University
• Susan Tilton (susan.tilton@oregonstate.edu) - Oregon State University (virtual)
• Rachel Kopec, (kopec.4@osu.edu) - The Ohio State University (virtual)
• Jacques Izard (jizard@unl.edu) - University of Nebraska-Lincoln (virtual)
• Pratibha Nerurkar (pratibha@hawaii.edu) - University of Hawaii (virtual)
• Silva Kolluri (siva.kolluri@oregonstate.edu) - Oregon State University (virtual)

Brief Summary of Minutes

Brief summary of minutes of the W5122 Multistate group annual meeting:

Thursday, October 12, 2023:

9:00 - 9:20 AM – Dr. Chris A. Pritsos, Director of Nevada Agricultural Experiment Station and W5122 lead administrator provided opening remarks and a presentation on the origin and organization of US Land Grant Institutions and Agricultural Experiment Stations, an update on NIFA/USDA Funding and resources including distribution of Hatch funds and the Multistate Research Funds Impacts website: www.mrfimpact.org.

Research update presentations (15 min presentation + 10-15 min Q&A and discussion)

9:30 - 10:00 AM: Nancy D. Turner from Michigan State University provided a research update on Diet Induced Perturbations in Distal Colon Microbiome and Metabolome Occur in Parallel with a Reduction in Early Colon Lesions. Identified higher Riboflavin likely increased by Prevotelaceae_Prevotella, which may be protective against colon cancer risk.

10:00 - 10:30 AM: Rachel Kopec from The Ohio State University provided a research update on her work leveraging state-of-the-art metabolite ID and multi-omic analyses with novel food processing techniques, specifically use of moderate electric field (MEF) exposure to sterilize food and increase bioavailability of organic (porphyrin-bound) iron and other heat-labile nutrients.

10:45 - 11:15 AM: Jacques Izard from the University of Nebraska Medical Center provided a research update on his work investigating Short Chain Fatty Acids Production Along the Digestive Tract, their impacts on inflammatory bowel disease and ulcerative colitis, and specifically how bioavailability of polyphenols is impacted by ostomy surgery (surgical removal intestinal sections) often performed as treatment for these and other intestinal diseases.

11:15 - 11:45 AM: Susan Tilton from Oregon State University provided a research update on her research on the utilization of an Organotypic Airway Model to Assess Role of Phytochemicals in Respiratory Disease. Specifically, how environmentally-relevant concentrations of polycyclic aromatic hydrocarbons found in cigarette smoke and other inhaled toxins are metabolized and impact lung tissue and carcinogenicity.

11:45 - 12:15 PM: Pratibha Nerurkar from the University of Hawaii provided a research update on her research on benefits of fermented foods via impacts on the gut microbiota and inflammatory state/immunomodulation, specifically the impacts of Kimchi – a Korean food made from fermented cabbage.

12:15 -1:15 PM: Siva Kolluri from Oregon State University provided a research update on his work investigating the anti-cancer effects of bioactive food components that impact aryl hydrocarbon Receptor (AhR)-mediated pathways to regulate anti-cancer functions. (virtual)

1:30 - 2:00 PM: Tiffany Weir from Colorado State University provided a research update on her work examining Microbial Pathways of Polyphenol Metabolism in the Human Gut for Impacts on Polyphenol Bioavailability following consumption of blueberry extracts in post-menopausal women with above normal blood pressure.

2:00 - 2:30 PM: Bill Helferich from the University of Illinois Urbana-Champaign provided historical perspective on 30 years of work by x-122 group members from soy to bacon on breast cancer growth and progression, then discussed his research on thermally abused frying oil on cancer risk via promoting metastasis and tumor angiogenesis.

2:30 - 3:00 PM: Chi Chen from the University of Minnesota presented an update on his investigation of the metabolism and bioactivity of the protein fermentation product p-cresol, noting general products (e.g., SCFAs, amines) and “special” products (indoles, phenols from AAA/p-cresol) that have antioxidant and possibly antidiabetic effects, while p-cresol sulfate is a uremic toxin.

3:15 - 3:45 PM: Adam Chicco from Colorado State University discussed a recent study that investigated the impact of Dietary Soybean Oil with and without Fish Oil on Serum PUFA Status of Malnourished Infants in Kenya, concluding that supplemental fish oil was not necessary to restore long-chain omega-3 polyunsaturated fatty acid status if adequate essential fatty acids (linoleic and linoleic acid) were provided as a soya blend.

3:45 - 4:15 PM: Efren Delgado from New Mexico State University discussed his research on optimizing methods for jujube microencapulation using cottonseed meal protein isolate as a carrier to supply polyphenolic compounds, which has demonstrated improved efficiency of encapsulation over the standard maltodextrin encapsulation approach. These retain higher phenolic content and antioxidant activity in vitro. Work demonstrates valuable use of cottonseed meal as an agro-industrial by-product contacting high protein concertation that can be used for functional foods and aquaculture feed.

4:15 - 4:45 PM: Hongbing Fan from University of Kentucky discussed his plans as a new faculty member at University of Kentucky Animal and Food Sciences Department to initiate new project investigating food-derived antihypertensive peptides – including chicken egg tripeptide on BP in SHR, perhaps by increasing activity of ACE2 activity, favoring BP reduction and less activity of ACE1 and classic RAAS hypertensive signaling. Also discussed new exploratory project investigating plant-based meat analogs as a source of bioactive peptides via peptidomics.

4:45 -5:15 PM Kaustav Majumder from the University of Nebraska-Lincoln discussed his work investigating how gamma-glutamyl peptides impact vascular inflammatory signaling through CasR, reduction of adhesion molecules and cytokines, and perhaps via altering the gut microbiome to reduce atherosclerotic lesions and macrophage infiltration into atherosclerotic plaques in mice.

6:30-9 PM: Group Dinner and Business Meeting at the Calistoga Inn, discussing ongoing and new collaboration opportunities and plans for W5122 group activities in 2024.

Discussion of new and emerging collaborative projects and initiatives

Dr. Weir is serving as a guest editor for two microbiome Frontiers journals special topic review series (Frontiers in Nutrition and Frontiers in Microbiome), to which at least 2 members plan to contribute. Other interested members should contact Tiffany for more information.

Various potential and ongoing research collaborations and shared interests were discussed based on research reports presented during the meeting, which we hope will promote continued productivity and interactions within our group and our institutions.

Discussed limiting member research updates to 2-3 slides demonstrating major advances and capabilities of their research to facilitate more interaction and discussion of collaboration potential at the next annual meeting.

Voted to hold next annual meeting in Calistoga or perhaps Lake Tahoe region in 2024, perhaps moving to Corvallis in 2025 to facilitate in-person participation from multiple group members at Oregon State University.

Accomplishments

Activities/Accomplishments: Objective 1: Examine the effects of phytochemicals and other dietary components on gut microbiota and intestinal function. W5122 researchers in Michigan (Turner) demonstrated beneficial changes in the colon microbiota of rats when a dried plum puree was included in the diet.  Changes in the microbiome occurring with development of colon cancer observed in rats consuming a polyphenol free diet are mitigated by inclusion of the dried plum puree in the diet.  Alterations in the microbiota also contributed to modifications in the fecal metabolome, and several compounds endogenous to plums were discovered in the luminal metabolome and microbial metabolites that were affected by the diet and disease state.  Several of the compounds present in rats consuming the dried plum puree diet have been shown to suppress proliferation and enhance apoptosis, to be involved in IL-10 signaling, as well as being important in cancer or tumor morphology.  Further analyses linking the microbiota with the metabolomics results indicated there is an association between 4 of the microbiota and the levels of riboflavin in the colon, and luminal riboflavin may suppress colon cancer.  These studies indicate that consuming bioactive compounds at levels obtainable with foods can enhance protection against intestinal disease, and that the benefit is partly derived through their effects on colonic microbiota and metabolic byproducts.  Changes in the microbial metabolome are associated with multiple pathways involved in inflammation and tumorigenesis W5122 researchers in Nebraska (Izard) investigated the biological consequences of ostomy, a life-saving surgery for severe gastrointestinal and medical conditions, such as Crohn’s disease, colitis, and colorectal cancer. However, many ostomates experience physical and emotional distress which significantly reduces their quality of life due to mechanisms that are not well understood. Over the past 12 months. Dr. Izard analyzed the concentrations of 8 short chain fatty acids (SCFAs) and lactic acid of ileostomy, colostomy, and control groups using LC-MS/MS. Results revealed the drastic change in concentrations of eight tested SCFAs and elevated lactic acid concentrations in ileostomates, but not in colostomates, compared to the control. Analyses of diet and symptom was also performed across the groups. This study provides valuable data for identifying biomarkers for future treatment and improving management of daily life for ostomates and can be expended to the general population. W5122 researchers in Indiana (Verma), in collaboration with Materials Science Engineers, has developed a sampling capsule that can collect intestinal contents from various parts of the gastrointestinal tract. They administered these capsules to pigs and demonstrated that they are able to collect samples from the small intestine or the large intestine, then compared the contents of the capsule to the contents of the sections of the gastrointestinal tract and highlighted that the microbiome composition is similar to the expected section. Thus, they confirmed the novel smart capsule performs well in vivo. The development of this capsule will help support future characterization of the microbiome across the gastrointestinal tract in healthy people and in people suffering from intestinal diseases, as well as help track the effects of various dietary components on the gut microbiome. W5122 researchers in Oregon (Tilton) investigated how the gut microbiota contributes to macrophage-mediated inflammation in adipose tissue with consumption of an obesogenic diet, thus driving the development of metabolic syndrome. There is a need to identify and develop interventions that abrogate this condition. The hops-derived prenylated flavonoid xanthohumol (XN) and its semi-synthetic derivative tetrahydroxanthohumol (TXN) attenuate high-fat diet-induced obesity, hepatosteatosis, and metabolic syndrome in C57Bl/6J mice. This coincides with a decrease in pro-inflammatory gene expression in the gut and adipose tissue, together with alterations in the gut microbiota and bile acid composition. We integrated and interrogated multi-omics data from different organs with fecal 16S rRNA sequences and systemic metabolic phenotypic data using a Transkingdom Network Analysis. Findings establish an important mechanism by which TXN mitigates adverse phenotypic outcomes of diet-induced obesity and metabolic syndrome. W5122 researchers in Colorado (Weir) have continued to examine both the effects of diet and direct microbiota modification (ie. probiotics) on intestinal and vascular health in both pre-clinical animal models and human clinical trials. In addition, Dr. Weir has begun to examine whether/how the microbiota influences individualized responses to phytochemical (specifically polyphenol) interventions. Their labs approach includes metagenomic sequencing of microbiomes from polyphenol intervention trials to look for carbohydrate degrading enzymes (CAZymes) that convert polyphenols to aglycone forms and also polyphenol metabolic pathways that can alter or degrade polyphenol compounds thought to be responsible for bioactivity. Understanding these interactions is critical to a deeper understanding of variability in “exposure” to bioactives from food and how they may be predictive of variations in response to diet interventions. W5122 researchers in California (Marco) continued their research examining the functional properties of microorganisms in fermented foods and digestive tract. Using dietary intake data and health biomarkers in the NHANES database, they showed that consuming, non-harmful (commensal) live microbes is modestly associated with reduced cardiometabolic disease risk. Fermented foods containing live microbes (such as yogurt, kefir, kimchi, and unpasteurized sauerkrauts) are the greatest contributors of live microbes in human diets. Lactic acid bacteria are essential to many food fermentations and are the most abundant microbes in those foods. They showed that exogenous quinones induce a hybrid metabolism resembling fermentation and respiration in the lactic acid bacteria species, Lactiplantibacillus plantarum. L. plantarum, a prominent microbe in food fermentations and for which certain strains are used as probiotics, can use quinones made by other lactic acid bacteria for this metabolism. Lastly, they showed that dietary resistant starch affects intestinal and bodily responses to L. plantarum intake, and vice versa. Synergistic, antagonistic, and additive effects were found on the gut microbiota, intestinal epithelium, and intestinal, serum, liver, and urinary microbiomes. In summary, fermented foods with live microbes are a major source of dietary microbes associated with good cardiovascular health. Lactobacilli in fermented foods perform diverse metabolisms that may be harnessed to improve fermentation performance. Habitual diet, and dietary fibers in particular, may affect the functionality of probiotics and other dietary live microbes to improve health. W5122 researchers in Indiana (Verma) continued their research in collaboration with colleagues from Materials Science Engineering to develop a sampling capsule that can collect intestinal contents from various parts of the gastrointestinal tract. They administered these capsules to pigs and demonstrated that they are able to collect samples from the small intestine or the large intestine, then compared the contents of the capsule to the contents of the sections of the gastrointestinal tract to highlight that the microbiome composition is similar to the expected section. Thus, the smart capsule performs well in vivo. The development of this capsule can help support future characterization of the microbiome across the gastrointestinal tract in healthy people and in people suffering from intestinal diseases. It can also help track the effects of various dietary components on the microbiome.   Objective 2: Identify cellular mechanisms and molecular targets of beneficial or adverse dietary components that influence human health. W5122 researcher in Connecticut (Chun) examined the effects of Blackcurrants on cardiovascular health among women in menopause transition. Previous cell and animal studies suggest that blackcurrant (BC; Ribes nigrum) can be a potential dietary agent that may mitigate oxidative stress and inflammation and improve dyslipidemia, thus reducing the risk of cardiovascular disease (CVD). The objective of this study was to examine the effects of the supplementation of BC anthocyanin (ACN) extract on CVD risk in healthy adult women in menopause transition and investigate the underlying mechanisms. The effects of BC ACN supplementation on blood pressure, anthropometrics, fasting blood lipids and biomarkers of oxidative stress and inflammation were evaluated using clinical, anthropometric measures and blood samples collected from a 3-arm, randomized, double-blind, placebo-controlled clinical trial in peri- and early postmenopausal women. Thirty-eight peri- and early postmenopausal women aged 45-60 years were randomly assigned into one of three treatment groups for six months: placebo (control group), 392 mg/day BC powder (low-BC group) and 784 mg/day BC powder (high-BC group). The significance of differences in outcome variables was tested by repeated-measures ANOVA with treatment and time as between- and within-subject factors, respectively. Overall, BC supplementation decreased fasting plasma triglycerides (TG), thiobarbituric acid reactive substances (TBARS) and interleukin-1β (IL-1β) compared to the control group (P < 0.05) without changes in body composition. The 6-month change in oxidized LDL was inversely correlated with 6-month change in catalase and ABTS (P < 0.05) while 6-month C-reactive protein (CRP) change was positively correlated with 6-month change in TG and IL-1β (P < 0.01). These findings suggest that daily BC consumption for six months may mitigate the risk of CVD, potentially through improving dyslipidemia, inflammation and lipid peroxidation and through antioxidant properties. Further studies of larger samples and population with higher risk for CVD are warranted to confirm these findings. W5122 researchers in Oregon (Tilton) completed studies examining the potential for supplementation with Brussels sprouts (BS) or 3,3'-diindolylmethane (DIM) to alter plasma levels of the environmental pollutant BaB and its metabolites over a 48-h period following micro-dosing with 50 ng (5.4 nCi) [14C]-BaP, likely by delaying BaP absorption. Although the number of subjects and large interindividual variation are limitations of this study, it represents the first human trial showing dietary intervention altering toxicokinetics of a defined dose of a known human carcinogen. W5122 researchers in Oregon (Tilton) completed studies utilizing primary human bronchial epithelial cells (HBEC) cultured in 3D at the air-liquid interface (ALI) as a physiologically relevant model to evaluate the effects of inflammation on toxicity of polycyclic aromatic hydrocarbons (PAHs), a class of contaminants generated from incomplete combustion of fossil fuels. Normal HBEC were differentiated in the presence of IL-13 for 14 days to induce a profibrotic phenotype similar to asthma. Cells were evaluated for cytotoxicity, barrier integrity, and transcriptional biomarkers of chemical metabolism and inflammation by quantitative PCR.  Cells with the IL-13 phenotype treated with BAP result in significantly (p<0.05) decreased barrier integrity, less than 50% compared to normal cells.  Interaction of BAP in the IL-13 phenotype was more apparent when evaluating transcriptional biomarkers of barrier integrity in addition to markers of mucus production, goblet cell hyperplasia, type 2 asthmatic inflammation and chemical metabolism, which all resulted in dose-dependent changes (p<0.05) in the presence of BAP. These data are the first to evaluate the role of combined environmental factors associated with inflammation from pre-existing disease and PAH exposure on pulmonary toxicity in a physiologically relevant human in vitro model. W5122 researchers in Oregon (Tilton) in collaboration with the FDA, the US EPA, and the NIH to procure chemicals for toxicity testing, generated a diverse chemical library of consumer products, food additives, industrial chemicals, pesticides, drugs, and chemical mixtures for which society has little or no safety information. As the project evolves, they will conduct RNA sequencing experiments to measure changes in the gene expression networks that the toxic chemicals provoke, and formulate hypotheses about which biomolecular targets the chemicals attacked initially and which pathways led to the observed endpoint. To test these hypotheses, they will edit the zebrafish genome via CRISPR/Cas9 to knock out or over-express critical genes, then repeat the exposures. W5122 researcher in Nebraska (Majumder) is examining the efficacy of dietary iso-peptides (γ-glutamyl peptide: γ-EV) in inhibiting vascular inflammation, atherosclerosis, and associated chronic metabolic disorders like type-2 diabetes. Study with atherosclerotic-prone male Apolipoprotein E knockout (ApoE-/-) mice with high fat diet (HFD: 40 kcal% fat, 1.25% cholesterol) showed that intervention of γ-EV reduces plaque development in the aorta, reduces vascular inflammation by reducing the expression of ICAM-1, VCAM-1, and LOX-1, reduced macrophage infiltration and inflammation in the atherosclerotic plaques (MOMA-2) in the aortic root, reduced expression of cytokine TNF-α and chemokine MCP-1 in the plasma. γ-EV can be detected (5.26mM) in blood plasma after oral administration, however, an estimated 60% of the ingested γ-EV remain unabsorbed and reach the colon intact, where they can possibly interact with the gut microbiota. 16s sequencing of the cecum content data showed increase the abundance of Akkermansia and decrease the abundance of Dubosiella after γ-EV intervention. qPCR testing further identified that γ-EV enrich the abundance of Akkermansia muciniphila in the cecum content. W5122 researchers in Colorado (Chicco) published a study demonstrating the impacts of dietary fatty acid intake during pregnancy on fetal development and metabolism using a novel ovine model of maternal-fetal metabolic programming. Studies demonstrated that elevated consumption of saturated fatty acids (~25% kcal intake) promoted skeletal muscle insulin resistance and enhanced uptake and oxidation of fatty acids in mid-term fetuses, consistent with findings from murine and non-human primate models. Additional studies established that supplementing 2% algae-derived DHA to the diet of pregnant ewes crosses the maternal rumen and placenta to enrich fetal tissue DHA levels. This was associated with complex shifts in the expression of fatty acid transporters on the placenta and fetal tissues that may impact nutrient metabolism during development and early neonatal life.  Taken together, these studies are the first to validate use of an ovine model for investigating the impact of maternal dietary fatty acid supplementation on fetal metabolism and development. W5122 researchers in Colorado (Chicco) worked in collaboration with groups from the University of Texas and the Kenya Medical Research Institute a study that investigated the effect of Corn Soy Blend plus Vegetable Oil (CSB-VO) supplements with or without Fish Oil (FO) on serum omega-3 fatty acids status and immunological patterns in Kenyan children aged 9 to 24 months with moderate acute malnutrition (MAM). Results demonstrated that children with MAM are significantly deficient in n3-PUFA measured by serum PLs, but not RBC PLs, and that 12 weeks of the current Kenyan standard of care supplement (CSB + VO) effectively normalizes serum PUFA status and reduces inflammatory markers. Supplemental FO provides little discernible benefit above that of CSB + VO on PUFA status, inflammation or clinical outcomes, indicating that MAM children are capable of converting dietary 18:3n3 into long chin-n3-PUFA, but are likely substrate limited without intervention.  Therefore, MAM children do not require pre-formed DHA or other LC-n3-PUFA to maintain a healthy serum n3/n6 ratio (VO is sufficient), though we cannot discount that higher or longer-duration FO supplementation might augment DHA enrichment and/or arachidonic displacement in serum and tissues.   Objective 3: Explore the interaction between dietary components and the host metabolome and epigenome. W5122 researchers in Minnesota (Chen) examined lipid oxidation products-elicited metabolic changes in gastrointestinal digesta after feeding oxidized soybean oil to nursery pigs. Consumption of fried food by humans and feeding recycled cooking oils to animals introduce significant amount of primary lipid oxidation products (LOPs), such as peroxidized fatty acids, and secondary LOPs, mainly lipidic aldehydes, into their gastrointestinal tracts (GIT), but the metabolic fates of those LOPs and their metabolic interactions with dietary components in the GIT are poorly understood. In the current study, oxidized lipids-elicited metabolic changes in the GIT were characterized by a nursery pig feeding trial and comprehensive metabolomic and biochemical analyses. Compared to soybean oil (CSO), Oxidized soybean oil (OSO) prepared by exposure to frying temperatures compromised the growth performance of nursery pigs in both weight gain and feed intake. OSO elevated the concentrations of lipidic aldehydes in all segments of the GI tract, especially nonanal, hexanal, and pentanal in cecum and colon. This observation was correlated with the increases of carbonylated protein in digesta. Besides direct influences of aldehydes, OSO decreased free amino acids and elastase activity in the small intestine and decreased short-chain fatty acids and bile acids in the large intestine. These results indicated that extensive influences of OSO on the digesta metabolome in the GI tract were caused by both direct contribution of LOPs and the metabolic interactions of LOPs with proteins, digestive enzymes, and microbiota. These observations provide insights into the metabolic fates of lipidic aldehydes and subsequent disruptions of nutrient and microbial metabolism and chemical environment in the GIT. W5122 researchers in Minnesota (Chen) also examined the temporal pattern of p-cresol production in infants, a microbial degradation product of the amino acid tyrosine. Previous studies have implicated p-cresol in multiple pathological events, including cytotoxicity in renal and cardiovascular systems and autistic symptoms in children. However, there is a paucity of information on p-cresol production in infants whose gut microbiomes are under development for producing functional metabolites. Methods: Total 250 fecal samples were collected from 138 healthy infants born at full-term at the ages of 1, 4, 12, and 24 weeks. The concentrations of p-cresol, HPAA, tyrosine, and other free amino acids were determined by dansyl chloride-based chemical derivatization and liquid chromatography-mass spectrometry-based metabolomic analysis. Results: Fecal concentrations of many free amino acids continuously increased from week 1 to 24 while the lowest concentrations of tyrosine were observed at week 4. Using ≥0.02 in HPAA/tyrosine and p-cresol/tyrosine ratios (2% conversion rate) as the cut-off value for tyrosine degradation activities, the formation of HPAA was detected in 21%, 28%, 41%, and 59% of infants at week 1, 4, 12, and 24, respectively, while p-cresol production only occurred in 0%, 6 %, 7%, and 17% of infants at week 1, 4, 12, and 24, respectively. Conclusions: All these observations show the gradual development of microbial tyrosine degradation activity, especially the reaction from HPAA to p-cresol, in infants, and warrant further investigation on the colonization of microbial species responsible for these reactions in early life. W5122 researchers in Colorado (Weir) are beginning to correlate metagenomic data of gut microbiomes with plasma metabolites to gain a deeper understanding of how the microbiome influences bioavailability and exposure to beneficial phytochemicals. Complementary experiments in germ free mice and those with human-associated gut microbes are being used to identify metabolites that directly result from microbial metabolism interactions.   Objective 4: Determine how food processing influences chemical composition to affect human health. W5122 researchers in New Mexico (Delgado) investigated how rapid detection of food-borne pathogens is a critical first step to abating health risks associated with food-borne pathogens. Together with the College of Engineering we tested a novel rapid detection platform based on fluorescence imaging that combines a user-friendly, portable loop mediated iso-thermal amplification (LAMP) reaction device and a smartphone-based detection system. We demonstrated that this platform was able to detect and quantify LAMP assay samples containing three different concentrations of Staphylococcus aureus from 109 CFU/mL down to 103 CFU/mL. S. aureus is one of the most important food-borne pathogens especially in dairy products and causes a wide range of clinical infection. W5122 researcher in Hawaii (Nerukar) provided evidence that the beneficial effects of fermentation on food chemical composition and positive influence on human health. In Hawaii, minority populations such as Native Hawaiians and Pacific Islanders (NHPI) have more than twice the rate of obesity-associated type 2 diabetes (T2D), as compared to Caucasians and more than five times as likely to die from T2D. Current therapies for obesity are complicated due to factors including an inability to maintain long-term weight loss and drug-drug interactions. In addition, conventional therapies may not be affordable, suitable and/or acceptable for culturally sensitive minority populations. There is a growing awareness and mounting body of scientific evidence, that successful implementation of strategies to control T2D among ethnic minorities will require culturally appropriate interventions.  Recent studies indicate the beneficial effects of fermentation on food chemical composition and positive influence on human health. Our studies have identified the influence of raw ingredients on health beneficial bacteria and corresponding metabolites in fermented foods such as kimchi. W5122 researchers in Minnesota (Chen) examined protein and lipid oxidation in soybean meals, a premier source of protein for feeding production animals. Protein oxidation negatively affects the nutritional value of SBM, but its causative associations with soybean oil extraction methods and non-protein components in SBM were not well examined. In the current study, 40 solvent extracted SBMs (SSBM) and 8 mechanically extracted SBMs (MSBM) collected from different commercial producers and geographic locations were profiled by chemometric analysis. The results showed that the extraction methods led to diverse differences between SSBM and MSBM. In gross composition, SSBM had greater crude protein, ash, moisture, and water activity while MSBM had greater crude fat and crude fiber. In protein oxidation, MSBM had greater protein carbonyl contents than SSBM (9.2 vs 5.2 mmol/kg protein, p<0.0001). In lipid oxidation, MSBM also had greater p-anisidine values than SSBM (1.25 vs 0.48, p<0.001), and more lipidic aldehydes, including 2-hexenal, 2-heptenal, 2,4-heptadienal, octanal, 2-octenal, 2-decenal, and nonanal. In antioxidant status, SSBM had greater Trolox equivalent antioxidant capacity (TEAC) than MSBM (25.0 vs 23.6 µmol/g, p<0.0001), which was in consistent with the total phenolics content (1.17 vs 0.86 mg caffeic acid equivalent/g, p<0.0001) and the total content of isoflavones, including genistin, genistein, daidzin, and daidzein (2147.0 vs 1481.8 µg/g, p<0.0001). Interestingly, MSBM had greater contents of tocopherols, including alpha- and gamma-tocopherol, than MSBM due to higher residual oil content. Pearson correlation analysis showed that protein carbonyl content was positively correlated with the p-anisidine value and total aldehydes, but inversely correlated with the TEAC value. Among antioxidants, total phenolics and isoflavones contents had inverse correlations with protein carbonyl content, total aldehydes, and p-anisidine value, respectively. Overall, extraction methods significantly affected gross composition, oxidation, and antioxidant status of SBMs. Lipidic aldehydes and phenolic antioxidants play counteracting roles in the oxidation of soy protein. W5122 researchers in Minnesota (Chen) examined the metabolic fate of deoxynivalenol in nursery pigs. Chronic exposure of deoxynivalenol (DON), a common trichothecene mycotoxin in corn and cereal grains, compromises feed intake, growth, immune response, and reproduction of production animals.  Chemical derivatization of DON through sulfonation has been developed as a mitigation approach to reduce the bioavailability of DON in animal feeds, but the exact impacts of sulfonation on the biotransformation and excretion of DON in animals were not well characterized. In this study, a total 48 nursery pigs were fed 4 experimental diets containing 1.2 ppm or 4.1 ppm DON with or without 0.25% NoTox™ Ultimate D additive, a sulfite-based sulfonation agent, for 21 days. DON metabolites in urine and fecal samples were determined by liquid chromatography-mass spectrometry analysis. The results showed that DON was completely metabolized in nursey pigs as it was not detected in urine and fecal samples. The sulfite additive led to the formation of three DON sulfonate (DONS) metabolites, and increased deepoxy-deoxynivalenol (DOM), a microbial metabolite of DON, in feces. In urine, sulfonation decreased DON-3-glucuronide and DON-15-glucuronide but increased DOM-3-glucuronide and DOM15-glucuronide. Overall, sulfonation decreased the absorption of free DON in nursery pigs, making it more available for gut microbes to form DOM, an inert metabolite, for excretion.   Grants awards (new and ongoing):  W5122 members and their labs were awarded over $18M in new grants during the 2022-23 period in addition to over $26M 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 support research from our group from this reporting period are listed below. <table width="0"> <tbody> <tr> <td width="124"> W5122 member </td> <td width="93"> Year </td> <td width="180"> Project Title </td> <td width="112"> Funding Agency </td> <td width="120"> US Dollars (approx.) </td> </tr> <tr> <td rowspan="3" width="124"> Nancy Turner (Michigan State University) </td> <td width="93"> 2020-2025 </td> <td width="180"> Food processing, technology, and safety workforce development:  Dual certificate and associate degree program.  </td> <td width="112"> USDA-AFRI </td> <td width="120"> $499,999.08 </td> </tr> <tr> <td width="93"> 2021-2023 </td> <td width="180"> Colon cancer protection derived from prunes.  </td> <td width="112"> California Prune Board </td> <td width="120"> $31,000 </td> </tr> <tr> <td width="93"> 2022-2023 </td> <td width="180"> Dried beans contribute to colon health through microbiota-mediated mechanisms. </td> <td width="112"> Northarvest Bean Association </td> <td width="120"> $19,999 </td> </tr> <tr> <td rowspan="6" width="124"> Mohit Verma (Purdue University) </td> <td width="93"> 2022-2023 </td> <td width="180"> Sentient Environment for Enhancing Resilience (SEER) for Sustainable Animal Agriculture </td> <td width="112"> Purdue University College of Agriculture </td> <td width="120"> $100,000 </td> </tr> <tr> <td width="93"> 2023-2025 </td> <td width="180"> A universal field-deployable test for measuring and predicting the spread of SARS-CoV-2 in any host species </td> <td width="112"> United States Department of Agriculture Animal and Plant Health Inspection Services </td> <td width="120"> $2,729,261 </td> </tr> <tr> <td width="93"> 2023-2024 </td> <td width="180"> Testbeds for microbial source tracking using microfluidic paper-based analytical devices </td> <td width="112"> Center for Produce Safety Grants Program </td> <td width="120"> $394,516 </td> </tr> <tr> <td width="93"> 2021-2023 </td> <td width="180"> Field-deployable biosensors for managing animal health </td> <td width="112"> Foundation for Food and Agriculture Research </td> <td width="120"> $900,000 </td> </tr> <tr> <td width="93"> 2022-2023 </td> <td width="180"> Point-of-care detection of African swine fever virus: a paper-based device for molecular diagnostics </td> <td width="112"> United States Department of Agriculture Animal and Plant Health Inspection Service </td> <td width="120"> $1,000,000 </td> </tr> <tr> <td width="93"> 2022-2023 </td> <td width="180"> Use case demonstration of a paper-based LAMP platform for plant pathogen detection </td> <td width="112"> Foundation for Food and Agriculture Research </td> <td width="120"> $64,850 </td> </tr> <tr> <td width="124"> Mohit Verma (Purdue University) </td> <td width="93"> 2023-2024 </td> <td width="180"> Prediction and Control of Holobiont Resilience via Microbiomes </td> <td width="112"> Supporting Partnering for Advanced Research Teamwork (SPARK) Program </td> <td width="120"> $100,000 </td> </tr> <tr> <td width="124"> Mohit Verma (Purdue University) </td> <td width="93"> 2022-2023 </td> <td width="180"> Smart capsule biosensors </td> <td width="112"> Eli Lilly Strategic Research Collaboration for Connected Solutions </td> <td width="120"> $3,099,592 </td> </tr> <tr> <td width="124"> Mohit Verma (Purdue University) </td> <td width="93"> 2022-2024 </td> <td width="180"> Rural Drinking Water Quality: Understanding the Microbiome of Well Water </td> <td width="112"> Agricultural Research and Extension Leading to Economic Development in Indiana Agriculture and Rural Communities </td> <td width="120"> $75,000 </td> </tr> <tr> <td width="124"> Mohit Verma (Purdue University) </td> <td width="93"> 2022-2023 </td> <td width="180"> Swallowable smart capsule for targeted gastrointestinal microbiome sampling </td> <td width="112"> NIH National Institute of Diabetes and Digestive and Kidney Diseases </td> <td width="120"> $185,242 </td> </tr> <tr> <td rowspan="3" width="124"> Maria Marco (University of California-Davis) </td> <td width="93"> 2021-2023 </td> <td width="180"> Impacts of milk microbiota composition on whey quality in California. </td> <td width="112"> California Dairy Research Foundation </td> <td width="120">   </td> </tr> <tr> <td width="93"> 2022-2026 </td> <td width="180"> PIG-PARADIGM: Preventing Infection in the Gut of developing Piglets-and thus Antimicrobial Resistance - by disentAngling the interface of DIet, the host and the Gastrointestinal Microbiome. </td> <td width="112"> Novo Nordisk Foundation </td> <td width="120">   </td> </tr> <tr> <td width="93"> 2021-2023 </td> <td width="180"> The yogurt matrix during digestion: benefits of milk composition and structure </td> <td width="112"> California Dairy Research Foundation </td> <td width="120">   </td> </tr> <tr> <td width="124">   </td> <td width="93">   </td> <td width="180">   </td> <td width="112">   </td> <td width="120">   </td> </tr> <tr> <td width="124"> Kaustav Majumder (University of Nebraska-Lincoln) </td> <td width="93"> 2022-2027 </td> <td width="180"> Evaluating the Efficacy of Dry Bean-Based Dietary-Glutamyl Peptides for Improvement of Metabolic Syndrome </td> <td width="112"> USDA Hatch Multistate Enhanced Program, Nebraska Agricultural Experiment Station (NEAES) </td> <td width="120"> $217,472 </td> </tr> <tr> <td width="124"> Kaustav Majumder (University of Nebraska-Lincoln) </td> <td width="93"> 2023-2024 </td> <td width="180"> Alfalfa Seed Utilization for Human Food </td> <td width="112"> Dept of Agriculture-ARS (USDA-ARS-NCAUR)   </td> <td width="120"> $133,441 </td> </tr> <tr> <td width="124"> Kaustav Majumder (University of Nebraska-Lincoln) </td> <td width="93"> 2023-2024 </td> <td width="180"> Development of Plant Protein-Based High-Value and Innovative Food Products from Nebraska Pulses </td> <td width="112"> Specialty Crop Block Grant Program, Nebraska Department of Agriculture </td> <td width="120"> $38,449 </td> </tr> <tr> <td width="124"> Kaustav Majumder (University of Nebraska-Lincoln) </td> <td width="93"> 2023-2024 </td> <td width="180"> Dry Edible Beans as an Efficacious Alternative for the Development of Fortified-Blended Foods for Food-Aid Program </td> <td width="112"> Specialty Crop Block Grant Program, Nebraska Department of Agriculture </td> <td width="120"> $55,767 </td> </tr> <tr> <td width="124"> Kaustav Majumder (University of Nebraska-Lincoln) </td> <td width="93"> 2021-2024 </td> <td width="180"> Elucidating the Health Beneficial Traits of Kernels of Maize Relatives Digested in the Human Gastrointestinal Tract </td> <td width="112"> USDA Agriculture and Food Research Initiative- NIFA   </td> <td width="120"> $500,000 </td> </tr> <tr> <td rowspan="5" width="124"> Adam Chicco (Colorado State University) </td> <td width="93"> 2021-2023 </td> <td width="180"> Feeding the starving heart in Barth Syndrome </td> <td width="112"> Barth Syndrome Foundation </td> <td width="120"> $82,000 </td> </tr> <tr> <td width="93"> 2021-2023 </td> <td width="180"> Tissue-specific role of FADS2 in dietary regulation of cardiometabolic risk </td> <td width="112"> Colorado Agricultural Experimental Station (USDA) </td> <td width="120"> $50,000 </td> </tr> <tr> <td width="93"> 2020-2023 </td> <td width="180"> Effects of Chronic High LET Radiation on the Human Heart </td> <td width="112"> Translational Research Institute for Space Health (TRISH/NASA) </td> <td width="120"> $864,878 </td> </tr> <tr> <td width="93"> 2022-2025 </td> <td width="180"> Evolutionarily conserved variations in menaquinone structure: Functional implications </td> <td width="112"> National Science Foundation  </td> <td width="120"> $528,000 </td> </tr> <tr> <td width="93"> 2019-2024 </td> <td width="180"> Cortical-Medullary Circuitry Preventing the Cardiovascular Consequences of Chronic Stress </td> <td width="112"> NIH/NHLBI </td> <td width="120"> $690,578 </td> </tr> <tr> <td width="124"> Tiffany Weir (Colorado State University)                 </td> <td width="93"> 2023-2024         </td> <td width="180"> Diet and microbiome interactions: application in posttraumatic stress disorder (D-MAPS) </td> <td width="112"> Immunology, Inflammation, and Infectious Disease (3i) Initiative and the Cumming Foundation </td> <td width="120"> $33,000       </td> </tr> <tr> <td width="124"> Tiffany Weir (Colorado State University) </td> <td width="93"> 2023-2025 </td> <td width="180"> Tetrasol: Effects of a Microalgae Extract Dietary Supplement on Gut Health, Anxiety, and Immune Function </td> <td width="112"> Mycrophyt, LLC </td> <td width="120"> $216,000 </td> </tr> <tr> <td width="124"> Tiffany Weir (Colorado State University) </td> <td width="93"> 2023-2025 </td> <td width="180"> Munispore: Examining Bacillus clausii on intestinal function and regularity. </td> <td width="112"> ADM/Deerland Enzymes and Probiotics </td> <td width="120"> $112,000 </td> </tr> <tr> <td width="124"> Tiffany Weir (Colorado State University) </td> <td width="93"> 2023-2024 </td> <td width="180"> Examination of the bi-directional interactions between phytocannabinoids and a human-associated gut microbiota. </td> <td width="112"> Institute for Cannabis Research </td> <td width="120"> $189,000 </td> </tr> <tr> <td rowspan="3" width="124"> Pratibha V Nerurkar (University of Hawaii) </td> <td width="93">   </td> <td width="180">   </td> <td width="112">   </td> <td width="120">   </td> </tr> <tr> <td width="93"> 2021-2026 </td> <td width="180"> Empowering Women and Underrepresented Undergraduates with Advanced Technology Research Training in Agriculture and Food Sciences </td> <td width="112"> AFRI-NIFA </td> <td width="120"> $440,367 </td> </tr> <tr> <td width="93"> 2018-2024 </td> <td width="180"> Specialty Crops: From Farm to Human Health </td> <td width="112"> USDA- ARS </td> <td width="120"> $80,000 </td> </tr> <tr> <td rowspan="5" width="124"> Efren Delgado (New Mexico State University) </td> <td width="93"> 2021-2024 </td> <td width="180"> Developing an Alliance for Training and Apprenticeship in Climate-Smart Agriculture (DATA-Ag) </td> <td width="112"> USDA-AFRI-AWT Program through UT at Arlington.   </td> <td width="120"> $124,852   </td> </tr> <tr> <td width="93"> 2021 -2024   </td> <td width="180"> Training of Next Generation Workforce for Smart Food Science and Agricultural Technology in the Digital Era (WorkFoS-Ag)   </td> <td width="112"> USDA-AFRI   </td> <td width="120"> $500,000 </td> </tr> <tr> <td width="93"> 2021 - 2023   </td> <td width="180"> Transcriptome analysis of Phytophthora blight (Phytophthora capsici) interaction and identifying genes involved in the infection process for early detection of infected plants </td> <td width="112"> NM Chile Association   </td> <td width="120"> $91,850   </td> </tr> <tr> <td width="93"> 10/01/2022 – 09/30/2025   </td> <td width="180"> Genetic dissection of Phytophthora capsici resistance in chile pepper using epigenomic and transcriptomic approaches </td> <td width="112"> New Mexico Department of Agriculture (NMDA) - Specialty Crop Grant Program (SCBGP) </td> <td width="120"> $102,562 </td> </tr> <tr> <td width="93"> 2021-2026   </td> <td width="180"> Bioprocessing of Agroindustrial By-products   </td> <td width="112"> Hatch-Proposal- US Department of Agriculture   </td> <td width="120"> $27,500   </td> </tr> <tr> <td width="124"> Tilton (PI) Oregon State University </td> <td width="93"> 2022-2024 </td> <td width="180"> Development of a 3D respiratory co-culture model for assessing toxicity to chemicals from wildfire smoke </td> <td width="112"> Center for Translational Environmental Health Research   </td> <td width="120"> $25,000 </td> </tr> <tr> <td width="124"> Tilton (PI) Oregon State University </td> <td width="93"> 2020-2025 </td> <td width="180"> Linking PAH Exposure to Health Outcomes Using Human Primary In Vitro Respiratory Model </td> <td width="112"> NIH/NIEHS P42 ES016465 </td> <td width="120"> $1,470,000 </td> </tr> <tr> <td width="124"> Tilton (PI) Oregon State University </td> <td width="93"> 2022-2024 </td> <td width="180"> Linking PAH Exposure to Health Outcomes Using Human Primary In Vitro Respiratory Model </td> <td width="112"> NIH/NIEHS P42 ES016465 Supplement </td> <td width="120"> $100,000 </td> </tr> <tr> <td width="124"> Tanguay (PI) Oregon State University </td> <td width="93"> 2020-2025 </td> <td width="180"> Predicting the Toxicity of Complex PAH Mixtures </td> <td width="112"> NIH/NIEHS P42 ES016465 </td> <td width="120"> $1,470,000 </td> </tr> <tr> <td width="124"> Tanguay (PI) Oregon State University </td> <td width="93"> 2021-2029 </td> <td width="180"> Discovering Chemical Activity Networks-Predicting Bioactivity Based on Structure </td> <td width="112"> NIH/NIEHS R35ES031709   </td> <td width="120"> $6,856,057 </td> </tr> <tr> <td width="124"> Tanguay (PI) Oregon State University </td> <td width="93"> 2020-2025 </td> <td width="180"> Pacific Northwest Center for Translational Environmental Health Research Zebrafish Core </td> <td width="112"> NIH/NIEHS P30ES030287 </td> <td width="120"> $5,605,000 </td> </tr> <tr> <td width="124"> Tanguay (PI) Oregon State University </td> <td width="93"> 2023-2028 </td> <td width="180"> Modernization of an Integrated Specific Pathogen Free Zebrafish Core Facility </td> <td width="112"> NIH/OD C06OD036081 </td> <td width="120"> $7,528,453 </td> </tr> <tr> <td width="124"> Maier (PI) Oregon State University </td> <td width="93"> 2023-2024 </td> <td width="180"> Trapped Ion Mobility Spectrometry Quadrupole Time-of-Flight System </td> <td width="112"> NIH/NIGMS S10OD032323 </td> <td width="120"> $1,345,698 </td> </tr> <tr> <td width="124"> Maier (PI) Oregon State University </td> <td width="93"> 2020-2025 </td> <td width="180"> Botanicals enhancing neurological and functional resilience in aging (BENFRA) Botanical Core </td> <td width="112"> NIH/NCCI U19AT010829 </td> <td width="120"> $1,896,860 </td> </tr> <tr> <td width="124"> Kolluri (PI) Oregon State University </td> <td width="93"> 2021-2024 </td> <td width="180"> Bcl-2 as a target in cancer </td> <td width="112"> NIH/NCI R21CA249627 </td> <td width="120"> $400,000 </td> </tr> <tr> <td width="124"> Chi Chen (Co-I); University of Minnesota </td> <td width="93"> 08/01/2020- 6/30/2024 </td> <td width="180"> Processed Food Intake, Metabolomics, and Adiposity </td> <td width="112"> NIH R01 </td> <td width="120">   </td> </tr> <tr> <td width="124"> Chi Chen (Co-I); University of Minnesota </td> <td width="93"> 0l/0l/2020- 12/31/2023 </td> <td width="180"> Lipocalin 2 as a regulator of phospholipid metabolism in adipose mitochondrial bioenergetics </td> <td width="112"> NIH R01 </td> <td width="120">   </td> </tr> <tr> <td width="124"> Chi Chen (Co-PI); University of Minnesota </td> <td width="93"> 1/1/2024-12/31/2027 </td> <td width="180"> Acquisition of Combustion Elemental Analyzer to Strengthen Agricultural Research at the University of Minnesota </td> <td width="112"> USDA </td> <td width="120">   </td> </tr> <tr> <td width="124"> Chi Chen (Co-PI); University of Minnesota </td> <td width="93"> 3/1/2023-2/28/2025 </td> <td width="180"> Advancing Biorefinery of Camelina and Pennycress Meal for Valuable Products </td> <td width="112"> Minnesota Forever Green Initiative </td> <td width="120">   </td> </tr> <tr> <td width="124"> Jacques Izard (University of Nebraska) </td> <td width="93"> 2018-2023 </td> <td width="180"> Digestive Tract Microbiome in Healthy Term Infants Receiving Mothers-Own Breast Milk or Cows Milk-Based Infant Formulas   </td> <td width="112"> Mead Johnson Nutrition </td> <td width="120">   </td> </tr> <tr> <td width="124"> Jacques Izard (University of Nebraska) </td> <td width="93"> 2021-2023 </td> <td width="180"> Attachment Security and the Gut-Brain Axis: A Nationwide Sample </td> <td width="112"> University of Nebraska ORED Biomedical Research Seed Grant </td> <td width="120">   </td> </tr> <tr> <td width="124"> Jacques Izard (University of Nebraska) </td> <td width="93"> 2018-2023 </td> <td width="180"> Improving phenotyping of human host in context of digestive tract microbiome studies for personalized nutrition </td> <td width="112"> Raikes Foundation via The Nebraska Food for Health Center </td> <td width="120">   </td> </tr> </tbody> </table>   Plans for 2024: W5122 researchers in Michigan (Turner) will finalize the analyses of the plum results comparing the effects in the proximal vs distal colon, continuing their project to explore the impact of baking on the chemopreventive capacity of sorghum, and will be resubmitting a NIH proposal to determine the impact of bioactives derived from dried beans on colon cancer. W5122 researcher in Nebraska (Izard) will further analyze the complexity of the interaction of the stool postbiotics with the clinical data acquired during the study of individuals with digestive resection, and investigate the role of the microbiota in this interaction in conjunction with diet. W5122 researchers in Indiana (Verma) plans on characterizing the gastrointestinal tract of the pigs in higher resolution to highlight the microbiome-metabolite relationships. W5122 researchers in Minnesota (Chen) will continue examining metabolic events associated with the exposure of oxidized lipids, bile acids, and phytochemicals; and will expand their chemometric analysis of oxidized soybean products and phenolic extracts after chemical and physical treatments. W5122 researchers in Colorado (Weir) aim to identify gut microbial metabotypes that predict polyphenol metabolism in the human gut and may aid in predicting individual differences in response to dietary interventions. W5122 researchers in California (Marco) plan to perform new studies investigating how fermented foods, and the microorganisms they contain, can improve intestinal health. W5122 researchers in Oregon (Tilton, Tanguay, Maier, Kolluri) will continue with studies on the adverse effects of dietary components and environmental toxicants on human health.  W5122 researchers in Connecticut (Chun) will conduct microbial analysis and metabolomics analysis to elucidate mechanisms of action for blackcurrant and CVD prevention related to lipid modification, oxidative stress and inflammation such bile acids, sterols, enterolactone, protocatechuic acid, gallic acid. W5122 researchers in Nebraska (Majumder) will expand the scope of their research by examining a broader range of dietary γ-glutamyl peptide variants. Through rigorous in-vitro experimentation, we seek to discern the nuanced effects and potential benefits associated with these diverse peptides, aiming to enhance our understanding of their individual and collective efficacies. Additionally, this study will delve into the specific involvement of Akkermansia and Dubosiella, unraveling their roles in the context of γ-glutamyl peptides. By elucidating the intricate interplay between these gut microbes and the peptides, we aspire to gain valuable insights into the underlying mechanisms that contribute to the observed efficacy, paving the way for more targeted and informed interventions in the future. W5122 researchers in Colorado (Chicco) will utilized a novel mouse model to examine the tissue-specific role of the FADS2 gene linked to cardiometabolic risk in humans on nutrient metabolism. They also plan to publish findings from their ovine model studies on DHA supplementation, and further develop ongoing collaboration with other W5122 members. W5122 researcher in Hawaii (Nerukar) will continue to explore the health-beneficial compounds of traditional fermented Hawaiian foods and further evaluate how food processing impacts their effects on obesity and glucose metabolism. W5122 researchers in New Mexico (Delgado) plans to work with the mill industry to develop a mathematical model to be used as a Distribution table in the milling process.

Publications

There were 71 new publications by W5122 members in 2022-2023 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 novel model systems.  Publications are listed below with W5122 group members in boldfaced text. <ol> <li>Pratibha V Nerurkar*, Jennifer Yokoyamaa, Kramer Ichimuraa , Shannon Kutschera, Jamie Wonga, Harry C Bittenbender, Youping Deng. Medium Roasting and Brewing Methods Differentially Modulate Global Metabolites, Lipids, Biogenic Amines, Minerals, and Antioxidant Capacity of Hawai'i-Grown Coffee (Coffea arabica). Metabolites, 2023 Mar 10;13(3):412. doi: 10.3390/metabo13030412.</li> <li>Gallegos-Ibanez, D, Jurado-Molina, J, Wedwitschka, H, Delgado E, Nelles, M.; Stinner, W. 2023. Ensiling of invasive Elodea sp., a novel aquatic biomass feedstock for the sustainable biogas production: effects of wheat straw and silage additives on silage quality and methane production. ACS Agricultural Science & Technology, DOI: 10.1021/acsagscitech.3c00043. </li> <li>Sapkota G, Delgado E, VanLeeuwen DF. Holguin OF, Flores N, Yao S. 2023. Preservation of Phenols, Antioxidant Activity, and Cyclic Adenosine Monophosphate in Jujube (Ziziphus jujuba Mill.) Fruits with Different Drying Methods. MDPI – Plants 12, 1804. https://doi.org/10.3390/plants12091804.</li> <li>Rodriguez Borbon, MI, Sohn, H, Delgado E, Fuqua, DO, Rodríguez Medina, A, Tlapa, D, Baez Lopez, Y. 2023. Shelf-Life Assessment on European Cucumber based on Accelerated Temperature-Humidity Stresses. Appl. Sci. 2023, 13, 2663. https://doi.org/10.3390/app13042663.</li> <li>Sapkota G, Delgado E, VanLeeuwen DF. Holguin O, Flores N, Heyduck R, Yao S. 2023. Dynamics of Nutrients in Jujube (Ziziphus jujuba Mill.) at Different Maturity Stages, Cultivars, and Locations. HortScience 58(2):155–163. <a href="https://doi.org/10.21273/HORTSCI16880-22">https://doi.org/10.21273/HORTSCI16880-22</a></li> <li>Thais M. Ramos, Hanna Louvau, Heesun Kim, Maria L. Marco, and Erin DiCaprio. 2022. Leveraging the COVID-19 fermentation trend to enhance nutrition and food safety extension efforts. Journal of Extension 60(4). Article 15. 10.34068/joe.60.04.15</li> <li>Zhengyao Xue and Maria L Marco. 2022. Improved assessments of bulk milk microbiota composition via sample preparation and DNA extraction methods. PLoS One 15:17(9) e0267992</li> <li>Colin Hill, Daniel J Tancredi, Christopher J Cifelli PhD, Joanne L Slavin, Jaime Gahche, Maria L Marco, Robert Hutkins, Victor L Fulgoni III, Daniel Merenstein, and Mary Ellen Sanders. 2023. Positive health outcomes associated with live microbe intake from foods, including fermented foods, assessed using NHANES database. Journal of Nutrition 153(3):1143-1149.</li> <li>Eric Stevens and Maria L Marco. 2023. Bacterial extracellular electron transfer in plant and animal ecosystems. FEMS Microbiology Reviews 19:47(3).</li> <li>Javad Barouei, Alice Martinic, Zach Bendiks, Darya Mishchuk, Dustin Heeney, Carolyn M Slupsky, and Maria L Marco. 2023. Type 2-resistant starch and Lactiplantibacillus plantarum NCIMB 8826 result in additive and interactive effects in diet-induced obese mice. Nutrition Research 118:12-28.</li> <li>Shuangping, Zhi-Feng Zhang, Jieqi Mao, Zhilei Zhou, Jing Zhang, Caihong Shen, Songtao Wang, Maria L Marco, Jian Mao. 2023. Integrated meta-omics approaches reveal Saccharopolyspora as the core functional genus in huangjiu fermentations NPJ Biofilms and Microbiomes. 9:65.</li> <li>Eric T. Stevens, Wannes Van Beeck, Benjamin Blackburn, Sara Tejedor-Sanz, Alycia R. M. Rasmussen, Mackenzie E. Carter, Emily Mevers, Caroline M. Ajo-Franklin, and Maria L. Marco. Lactiplantibacillus plantarum uses ecologically relevant, exogenous quinones for extracellular electron transfer. mBio 14(6):e0223423.</li> <li>Maier MLV, Siddens LK, Pennington JM, Uesugi SL, Labut E, Vertel EA, Anderson KA, Tidwell LG, Tilton SC, Ognibene TJ, Turteltaub KW, Smith JN, Williams DE. 2023. Impact of Phenanthrene Co-Administration on the Toxicokinetics of Benzo[a]pyrene in Humans. UPLC-Accelerator Mass Spectrometry Following Oral Microdosing. Chemico-Biological Interactions. 382:110608. doi: 10.1016/j.cbi.2023.110608. PMID: 37369263 </li> <li>Rude CI, Tidwell LG, Tilton SC, Waters KM, Anderson KA, Tanguay RL. 2023. Coupling Environmental Whole Mixture Toxicity Screening with Unbiased RNA-Seq Reveals Site-Specific Biological Responses in Zebrafish. Toxics. 11(3). doi: 10.3390/toxics11030201. PMCID: PMC10053777.</li> <li>Vermillion Maier ML, Siddens LK, Pennington JM, Uesugi SL, Tilton SC, Vergel EA, Anderson KA, Tidwell LG, Ognibene TJ, Turteltaub KW, Smith JN, Williams DE. 2023. Benzo[a]pyrene toxicokinetics in humans following dietary supplementation with 3,3’-Diindolylmethane (DIM) or Brussels sprouts. Appl. Pharmacol. 460:116377. doi: 10.1016/j.taap.2023.116377. PMCID: PMC9946811. (4.219)</li> <li>Rivera BN, Ghetu C, Chang Y, Truong L, Tanguay RL, Anderson KA, Tilton SC. 2022. Leveraging multiple data streams for prioritization of mixtures for hazard characterization. Toxics: Risk Assessment on Toxicity of Chemical Mixtures. 10:651. doi.org/10.3390/toxics10110651. PMCID: PMC9699527.</li> <li>St Mary L, Truong L, Bieberich AA, Fatig RO 3rd, Rajwa B, Tanguay RL. 2023. Comparative analysis between zebrafish and an automated live-cell assay to classify developmental neurotoxicant chemicals. Toxicol Appl Pharmacol. 2023 Oct 1;476:116659. doi: 10.1016/j.taap.2023.116659.</li> <li>Green AJ, Truong L, Thunga P, Leong C, Hancock M, Tanguay RL, Reif DM. 2023. Deep autoencoder-based behavioral pattern recognition outperforms standard statistical methods in high-dimensional zebrafish studies. 2023 Sep 17:2023.09.13.557544. doi: 10.1101/2023.09.13.557544.</li> <li>Dasgupta S, LaDu JK, Garcia GR, Li S, Tomono-Duval K, Rericha Y, Huang L, Tanguay RL. 2023. A CRISPR-Cas9 mutation in sox9b long intergenic noncoding RNA (slincR) affects zebrafish development, behavior, and regeneration. oxicol Sci. 2023 Jul 28;194(2):153-166. doi: 10.1093/toxsci/kfad050.</li> <li>McClure RS, Rericha Y, Waters KM, Tanguay RL. 2023. 3' RNA-seq is superior to standard RNA-seq in cases of sparse data but inferior at identifying toxicity pathways in a model organism. Front Bioinform. 2023 Jul 27;3:1234218. doi: 10.3389/fbinf.2023.1234218.</li> <li>Wilson LB, Moran IL, Anderson KA, Tanguay RL. 2023. 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Impact Statements

W5122 researchers in New Mexico (Delgado) demonstrated that a portable loop mediated iso-thermal amplification (LAMP) reaction device and a smartphone-based detection protocol is faster than PCR-based detection for rapid detection of food-borne pathogens - as the reaction is performed under isothermal conditions and completed in one hour or less.

Date of Annual Report: 03/14/2025

Report Information

Annual Meeting Dates: 10/02/2024 - 10/04/2024
Period the Report Covers: 10/06/2023 - 10/02/2024

Participants

Participants at the 2024 W5122 Annual Meeting are listed below, as well as in attached complete Annual Report.

Chi Chen (chichen@umn.edu) - University of Minnesota

Adam Chicco (adam.chicco@colostate.edu) - Colorado State University

Ock Chun (ock.chun@uconn.edu)- University of Connecticut

Efren Delgado (edelgad@nmsu.edu) - New Mexico State University (virtual)

Hongbing Fan (Hongbing.Fan@uky.edu) - University of Kentucky

Steve Frese (sfrese@unr.edu) - University of Nevada, Reno

Jacques Izard (jizard@unmc.edu) - University of Nebraska-Lincoln (virtual)

Rachel Kopec (kopec.4@osu.edu) - The Ohio State University

Claudia Maier (claudia.maier@oregonstate.edu) - Oregon State University

Kaustav Majumder (kaustav.majumder@unl.edu) – University of Nebraska-Lincoln

Maria Marco (mmarco@ucdavis.edu) - University of California-Davis

Pratibha Nerurkar (pratibha@hawaii.edu) - University of Hawaii (virtual)

Chris Pritsos (pritsos@unr.edu) - University of Nevada, Reno

Susan Tilton (susan.tilton@oregonstate.edu) - Oregon State University

Brief Summary of Minutes

Brief summary of minutes of the W5122 annual meeting:

Thursday, October 3, 2024:

8:35 - 9:00 AM – Dr. Chris A. Pritsos, Director of Nevada Agricultural Experiment Station and W5122 lead administrator provided opening remarks and a presentation on the FY24 Appropriations request, AFRI update, Farm Bill recommendations for Hatch Act, food and agriculture sciences education and research facilities act, along with an update on NIFA/USDA Funding, distribution of Hatch funds and the Multistate Research Funds Impacts website: www.mrfimpact.org.

Research update presentations (15 min presentation + 10-15 min Q&A and discussion)

9:00-9:35; Ock Chun (University of Connecticut) provided an update on her work investigating impacts of Blackcurrant (BC) extracts in postmenopausal women complemented by cell and animal models, including results of a clinical trial published this year in Nutrients. Dr. Chun’s research identified microbiome markers of osteoporosis risk and reported effects including beneficial impacts on blood lipids and oxidative stress without changing body composition, reduced CVD risk biomarkers, improved bone mineral density and increases in SFCA and phytoestrogen metabolites, suggesting links to the “gut-bone” axis that will be further explored in a pending USDA randomized clinical trial (submitted August 2024).

9:35-10:00; Efren Delgado from New Mexico State University discussed his research on food bioengineering technologies and agroindustry byproducts, including a USDA proposal with Oregon State University and NMSU for moving toward zero waste food manufacturing and using ag byproducts (e.g., cottonseed meal) to advance bioeconomy and rural/Tribal development in Southern New Mexico. This includes adding value to use of byproducts for producers and communities by developing of bio-based products and bioenergy education courses.

10:15-10:40; Jacques Izard from the University of Nebraska Medical Center provided a research update on his work investigating Short Chain Fatty Acids Production Along the Digestive Tract, their impacts on inflammatory bowel disease and ulcerative colitis, and specifically how bioavailability of beneficial serum and stool metabolites is impacted by ostomy surgery (surgical removal intestinal sections) often performed as treatment for these and other intestinal diseases.

10:45-11:10; Steve Frese from the University of Nevada, Reno (new W5122 group member) provided an overview of his research developing probiotics for preterm infants and development of the WOLFPACK Study (“Wide Open Local Fecal sample collection comparing Pharmaceutical intake, ACtivity, and dietary intaKe”), which seeks to understand how the gut microbiome of Northern Nevadans is affected by diet, health, lifestyle, and other factors. He also discussed a new undergraduate student summer training program at UNL Lake Tahoe campus on health implications of the gut microbiome, involving performance and analysis of DNA extractions, PCR, food frequency questionnaires, and a ‘lifestyle survey’, and providing educational feedback on dietary habits and health (200 enrolled to date, 61% female, 36+/- 15 yo, 25+/-5 BMI; 61% white). Descriptive studies are complimented with fecal culture experiments with different dietary ingredients (e.g., fiber from hemp, yeast- vs bovine-derived whey protein) to determine impacts on gut microbiota growth and SCFA production.

11:15-11:40; Maria Marco from the University of California-Davis reviewed her efforts and aims of large scale EATLAC educational and scientific program to educate public and scientific community on fermented foods and their benefits, which was the subject of a recent review article which she co-authored in Nature Reviews. She also discussed a transwell in vitro intestinal barrier function model she developed to investigate impacts of lab and commercial cabbage ferments on cytokines and barrier function. Recent studies found that the fermented foods reduced leaky gut (improved barrier integrity), lowered inflammatory cytokines and altered levels of lactate metabolites. Interestingly, while the lactate metabolites alone did not reduce cytokines, they did improve barrier function in this model.

11:45-12:10; Rachel Kopec from Ohio State University provided an overview of her research interests/expertise and technical competencies/capacities for examining dietary bioactive interactions, novel metabolite ID, and multi-omic integration to foster collaboration opportunities across the multi-state groups. She also discussed her in vitro digestion and intestinal uptake model using caco-2 cells and micellarized compounds and a recent collaboration with food engineers and sensory scientists to innovate food processing techniques that enrich plant foods with iron (e.g., synthesis of iron chlorophyll (replacing Mg++) to improve absorption of iron from foods like Kale). She found that engineering foods using some forms of protein (e.g., whey or legumes protein) bound to iron could improve absorption. Finally, she discussed her interest in integrating metabolomics and lipidomics into member research projects through collaborations to build a bigger omics toolbox and dataset integration across the multistate group.

1:15-1:40; Pratibha Nerurkar from the University of Hawaii discussed her work on the benefits of nanobubble (supra-oxygenated) water on the growth and metabolites/mineral contents of sprouts and microgreens, which improves productivity (lettuce and fruits yield) over standard aerated water. Potential collaboration with Efren Delgado were discussed for using nanobubbling for agricultural food sterilization/cleaning.

1:45-2:10; Claudia Maier from Oregon State University discussed her role and expertise as the PI of the OSU Biomolecular Mass Spectrometry center, and her research focusing on the characterization of botanicals and extracts, QC and standardization, and computational modeling in the context of cardiovascular, cardiometabolic, and neurodegenerative disease. Specific projects evaluating use of botanical extracts during the non-beta-amyloid accumulation mode of Alzheimer’s disease, LC-MS method development and cross-validation; metabolism of Ashwagandha constituents by gut microbiota, and spatial MS molecular analysis with 5 µm resolution were also discussed. The latter presentation sparked a new collaboration between Dr. Maier and Dr. Chicco to investigate the tissue-specific effects of dietary PUFA metabolism on eicosanoid/oxylipid production in the context of cardiometabolic risk in 2025-26 using CO AES funds.

2:15-2:40 PM; Susan Tilton from Oregon State University provided an update on her work, as part of the Super Fund Research Center, to study emerging health risks of polycyclic aromatic hydrocarbon (PAH) toxicity using a 3D airway organotypic (air-liquid interface) culture model consisting of primary human bronchial epithelial cells. Results are being used to elucidate the impacts of BAP metabolites and cellular communication and cell signaling and a pathway-based classification approach for predicting PAH-induced cancer.

3:30-3:55 PM; Chi Chen from the University of Minnesota provided an overview of his laboratory’s capabilities for quantifying levels of metabolites associated with health risks in humans, specifically three metabolites: urinary NAT n-acetyl-taurine (marker of hyperacetatemia), lipid aldehydes (markers of oxidative stress), and Cinnamoylglycine (identified as a negative predictor of diabetes risk in serum from participations in CARDIA study).

4:00-4:25 PM; Kaustav Majumder from the University of Nebraska-Lincoln provided an overview of his laboratory capabilities and research interests, elaborating on recent studies investigating Maize kernel bioactivities and how these may be impaired by domestication. In particular, he emphasized nutrients we have lost through “improvement” of modern maize agriculture – specifically higher CHO and lower protein content, and lower anti-inflammatory and antioxidant activities compared to landraces (early ag) and teosinte (ancient) maize varieties.

4:30-4:55 PM; Hongbing Fan from the University of Kentucky provided an overview of his new lab and developing research program, specifically discussing his work on preparing low molecular weight collagen peptides from carp fish (AFRI seed grant) as beneficial supplement for improving bone and skin health, including studies on GI absorption (Caco cells) and bioactivities (bone cells). He also discussed work on a project investigating the protective effects of ACE2-regulating peptides on development of aneurysms in a rodent model.

5:00-5:25 PM; Adam Chicco from Colorado State University provided an overview of the technologies and resources he is using to investigate the nutri-genetic impacts of essential fatty acid metabolism on cardiometabolic risk, including a novel Fads2 LoxP mouse model that he will cross with tissue-specific Cre recombinase mice for conditional deletion of the Fads2 enzyme encoding the rate limiting step in long-chain polyunsaturated fatty acid synthesis. Recent work with global Fads2 transgenic and knockout model have linked this enzyme to higher and lower myocardial injury following an index ischemia (heart attack), which appears to be associated with altered cardiac mitochondrial calcium buffering capacity. Future studies will investigate whether these effects result from cardiac-specific Fads2 activity, or transport of lipids derived from liver Fads2 activity using the Fads2LoxP mouse. These studies will be expanded to investigate effects of Fads2 on the eicosanoid/oxylipin profile in collaboration with Claudia Maier (W5122 member).

Friday, October 4, 2024:

8:30-11:00 Business Meeting/Working Breakfast in Granlibakken Granhall

Discussion of new and emerging collaborative projects and initiatives

Assigned W5122 group leadership roles for 2025

Reviewed guidelines for assembly of the Annual Report

Voted on location for next year’s meeting – Granlibakken Tahoe again in 2025, then perhaps Corvallis with Susan Tilton hosting in 2026.

Accomplishments

Activities/Accomplishments: Objective 1: Examine the effects of phytochemicals and other dietary components on gut microbiota and intestinal function. W5122 researchers in Nebraska (Izard) examined how milk fat globule membrane (MFGM) in infant formula affects gut bacteria and immune markers in newborns. Infants received either standard formula, MFGM-enriched formula, or breast milk for 60 days. Results showed that formula-fed infants had greater gut bacterial diversity than those fed breast milk, with more specific bacteria like Bifidobacterium. The MFGM-enriched formula led to increased beneficial fatty acids, although overall changes in gut bacteria and immune responses were modest compared to breast milk. W5122 researchers in Indiana (Verma), used pigs to study the biogeography of microbiome distribution across the GI tract. We collected contents from the following sections: duodenum, jejunum, ileum, cecum, ascending colon, transverse colon, and descending colon. They analyzed these contents for the microbiome composition and menaquinone distribution and thus, provided a map of the GI tract in a new way. These data can be used in the future to determine how diet or disease-driven perturbations impact the microbiome and metabolism. W5122 researchers in California (Marco) continued their work on probiotics, including providing guidance on reporting in probiotics clinical trials in systematic reviews and meta-analyses and publishing their findings on how consumption of probiotic lactobacilli in fermented milk can affect host responses compared to when consuming the probiotic in a supplement (non-nutritive) food. This work was complimented by studies designed to assess how encapsulation can be used to improve the delivery of peptides made by probiotic lactobacilli. Similarly, their studies provided fundamental knowledge on bile acid metabolism and provided pathways towards new probiotics based on specific metabolic capacities. Lastly, their investigations led to several important reviews on fermented foods broadly and fermented foods specifically (Brassica and beer). W5122 researchers in Colorado (Weir) completed 2 clinical nutrition interventions and have an additional intervention underway. They examined the impact of insect-deived fiber on the gut microbiome and symptom severity in individuals with IBS. We found that incorporating 4g/day of cricket-derived chitin into the diet was safe and tolerable in the target population, decreased gastrointestinal symptoms, and reduced systemic inflammation- potentially through stabilization of the gut microbiota. They also explored the gut and mental health effects of a microalgae extract from Tetradesmus obliquus (TOME). TOME intervention for 4 weeks improved gastrointestinal symptoms, mental health assessments, and reduced biomarkers of stress, anxiety, and disrupted gut barrier function. A third intervention, examining the impacts of a spore-based probiotic, Bacillus clausii, on gut health and immunity is currently underway and expected to be completed in March 2025. W5122 researchers in Colorado (Weir) continued to conduct animal experiments and mine clinical and pre-clinical datasets to understand how the gut microbiome interacts with specific dietary components (specifically, polyphenols, methylamines, and cannabinoids). We completed an animal study looking at bidirectional interactions between CBD/CBG and the gut microbiome in human microbiota-associated gnotobiotic mice. They found that both cannabinoids alter gut microbiota composition, but the microbiota does not appear to influence bioavailability of cannabinoids. In contrast, methylamine and polyphenol exposure does appear to rely on type and degree of metabolism by the gut microbes. W5122 researchers in Oregon (Maier) continued their studies on Xanthohumol (XN), a polyphenol found in the hop plant (Humulus lupulus) with antioxidant, anti-inflammatory, prebiotic, and anti-hyperlipidemic activity. Their own and the work of others provided preclinical evidence that suggested, that the gut microbiome is essential in mediating these bioactivities; however, relatively little is known about XN's impact on human gut microbiota in vivo. They and collaborators conducted a randomized, triple-blinded, placebo-controlled clinical trial (ClinicalTrials.gov NCT03735420) for determining safety and tolerability of XN in healthy adults. Thirty healthy participants were randomized to 24 mg/day XN or placebo for 8 weeks. As secondary outcomes, quantification of bacterial metabolites and 16S rRNA gene sequencing were utilized to explore the relationships between XN supplementation, gut microbiota, and biomarkers of gut health. Although XN did not significantly change gut microbiota composition, it did re-shape individual taxa in an enterotype-dependent manner. High levels of inter-individual variation in metabolic profiles and bioavailability of XN metabolites were observed. Moreover, reductions in microbiota-derived bile acid metabolism were observed, which were specific to Prevotella and Ruminococcus enterotypes. Their results suggest interactions between XN and gut microbiota in healthy adults are highly inter-individualized and potentially indicate that XN elicits effects on gut health in an enterotype-dependent manner.   Objective 2: Identify cellular mechanisms and molecular targets of beneficial or adverse dietary components that influence human health. W5122 researchers in Oregon (Tilton) completed studies on PAHs derived from combustion of carbon (coal, diesel, paving sealants, tobacco, wood-stoves, tires, paving sealants, etc.), that are important environmental pollutants found in the diet. Benzo[a]pyrene (BaP), the most studied PAH, is classified by the International Agency for Research on Cancer as a class 1 known human carcinogen. An estimated 95% of BaP exposure (non-occupational; nontobacco) is dietary ranging from 160-1600 nanograms daily.  Current risk assessments for environmental carcinogens rely on animal studies utilizing doses orders of magnitude higher than actual human exposures. In addition, risk assessments do not adequately account for combined exposures.  Studies utilizing the extremely high sensitivity of accelerator mass spectrometry (AMS) measured the toxicokinetcs of two common PAHs in mixtures, BaP and phenanthrene (Phe), in human plasma after exposure.  Overall, Phe was shown to be a competitive inhibitor of the major hepatic cytochrome P-450 (CYP) responsible for metabolism of BaP and these studies were the first to provide evidence that, at actual environmental levels of exposure, the toxicokinetics of BaP in humans is markedly altered by the presence of a second PAH.  Additional studies modeling the interaction of PAHs in mixtures found that standard models for chemical interactions generally underestimate toxicity across dose suggesting the potential for non-additive interactions of components.  Further studies evaluating the potential for benzo[a]pyrene toxicity in an in vitro model of chronic inflammation concluded that individuals with pre-existing disease may be more susceptible to toxicity and disease outcomes. W5122 researchers in Oregon (Maier) applied a computationally assisted analytical strategy combining fractionation of a Centella asiatica extract with HTS mass spectrometry and read-out from a MC65 bioassay for discovering and identifying constituents of C. asiatica that protect against Aβ cytotoxicity in vitro. Human neuroblastoma MC65 cells were exposed to subfractions of an aqueous extract of C. asiatica to evaluate the protective benefit derived from these subfractions against amyloid β-cytotoxicity. The % viability score of the cells exposed to each subfraction was used in conjunction with the intensity of the molecular features in two computational models, namely Elastic Net and selectivity ratio, to determine the relationship of the peak intensity of molecular features with % viability. We also overlaid mass spectral data obtained for each fractions with MC65 protection observed for each fractions and visualized the multi-dimensional information in a GNPS molecular network. Both computational methods unequivocally identified di-caffeoylquinic acids as providing strong protection against Aβ-toxicity in MC65 cells, in agreement with the protective effects observed for these compounds in previous preclinical model studies. They also showed in associated collaborative research that C. asiatica and its caffeoylquinic acids and triterpene constituents increase dendritic arborization of mouse primary hippocampal neurons and improve age-related locomotion deficits in Drosophila. Prior to use C. asiatica extracts were characterized by untargeted MS-based profiling and phytochemical marker compounds quantified by LC-MS-MRM-MS to ensure use of standardized extracts to ensure high reproducibility of the studies.  Taken together, this research provides support that caffeoylquinic acids and triterpenoids, both present in C. asiatica aqueous extracts, are bioactive constituents that are associated with in vitro observed antioxidant protective mechanisms and neurotrophic activity. Their preclinical studies show and confirm health promoting effects in aging relevant preclinical models of cognitive function and locomotion, but dependency on sex, mode of administration and dose was observed. W5122 researchers in Oregon (Kolluri) discovered a novel pathway to convert Bcl-2 from a cancer protective to a cancer destructive protein. Based on this discovery, we have screened chemical libraries and identified drug candidates that cause conversion of Bcl-2 from a cancer cell protective protein to a cancer cell killer protein. These compounds are designated here as ‘Bcl-2 functional converters’. W5122 researchers in Nebraska (Majumder) investigated the efficacy of dietary iso-peptides, specifically γ-glutamyl peptide (γ-EV), in mitigating vascular inflammation, atherosclerosis, and associated metabolic disorders like type 2 diabetes. Studies using atherosclerosis-prone male Apolipoprotein E knockout (ApoE-/-) mice fed a high-fat diet (HFD: 40 kcal% fat, 1.25% cholesterol) revealed that γ-EV intervention reduces aortic plaque development, decreases vascular inflammation by downregulating ICAM-1, VCAM-1, and LOX-1 expression, and lowers macrophage infiltration (MOMA-2) in atherosclerotic plaques at the aortic root. Additionally, γ-EV reduces plasma levels of pro-inflammatory cytokine TNF-α and chemokine MCP-1.  Following oral administration, γ-EV is detected in blood plasma at a concentration of 5.26 µM. However, approximately 60% of ingested γ-EV remains unabsorbed, reaching the colon intact, where it may interact with gut microbiota. 16S rRNA sequencing of cecal content indicates an increase in Akkermansia abundance and a decrease in Dubosiella after γ-EV intervention. Further qPCR analysis confirms γ-EV enrichment of Akkermansia muciniphila in the cecum, suggesting a potential gut microbiota-mediated mechanism for its vascular benefits. W5122 researchers in Colorado (Chicco) generated a Fads2LoxP mouse that will facilitate conditional targeting of the Fads2 gene encoding Delta-6 desaturase, the rate limiting enzyme in biosynthesis of long-chain polyunsaturated fatty acids from dietary essential oils. This model will  enable experimental testing of hypothesized nutri-genetic interactions between dietary omega-3 and omega-6 fatty acids with FADS2 expression on cardiometabolic risk in humans, based on accumulating evidence from epidemiological studies of FADS2 polymorphisms across diverse human populations, and potent effects of modulating global Fads2 expression and/or D6D activity in murine models of ischemic heart injury. W5122 researcher in Kentucky (Fan) is beginning research that aims to extract locally-sourced hemp seed proteins using a simple alkaline extraction method, then using different proteases to digest these proteins into bioactive peptides and compared their inhibition of ACE, the key enzyme contributing to high blood pressure. These proteases, including alcalase, thermoase, pepsin, flavorzyme, papain, thermolysin, have shown enormous potential in preparing peptides inhibiting the ACE activity, with thermolysin being the most potent. W5122 researcher in New Jersey (Bello) initiated a project to characterize the metabolic impacts of long term dosing of kratom alkaloids. The primary purpose of the experiments conducted during this period was to examine whether chronic oral dosing of a standardized alkaloid enriched-kratom extract (KE) prevented weight gain in diet-induced obese mice . The secondary purpose was to determine whether acute human equivalent doses of KE and major alkaloid, mitragynine (MTG), differentially influence cardiopulmonary measures in normal weight or obese mice. Overall, preliminary findings do not support the use of kratom alkaloid extract in diet-induced obesity prevention, but do suggest effects of kratom products on hemodynamic measures related to weight gain in mice.    Objective 3: Explore the interaction between dietary components and the host metabolome and epigenome. W5122 researchers in Connecticut (Chun) assessed the effects of blackcurrant (BC) anthocyanins on concentrations of microbial-derived short-chain carboxylic acids (SCCAs) and metabolites of phytoestrogens. They then examined associations with six-month changes in whole-body bone mineral density (BMD) and biomarkers of bone metabolism. Fecal and blood samples from a pilot randomized controlled trial were collected and analyzed from 37 eligible peri- and early postmenopausal women aged 45–60 years who were randomized into one of three treatment groups consuming one placebo capsule (control), 392 mg BC (low BC) or 784 mg BC (high BC) daily for six months. Significant differences were observed between groups at baseline in acetic, propionic, valeric, caproic and heptanoic acids (p < 0.05). Isobutyric acid significantly decreased from baseline (0 months) to six months in the control group (p < 0.05) and the high BC group had a significantly greater concentration than the control group at six months (p < 0.05). Butyric acid was significantly greater in the high BC group than low BC at six months (p < 0.05). Six-month changes in caproic and isobutyric acids showed weak correlations with changes in whole-body BMD (r = 0.3519, p < 0.05 and r = 0.3465, p < 0.05, respectively). Isovaleric and valeric acids displayed weak correlations with BALP (r = 0.3361, p < 0.05) and OPG (r = 0.3593, p < 0.05), respectively. Enterodiol was positively correlated with BALP (r = 0.6056, p < 0.01) while enterolactone was positively correlated with osteocalcin (r = 0.5902, p < 0.001) and negatively correlated with sclerostin (r = −0.3485, p < 0.05). The results suggest that BC may be a potential dietary agent to reduce postmenopausal bone loss through modulating microbially-derived SCCAs and phytoestrogen metabolites. W5122 researchers in Minnesota (Chen) characterized urinary N-acetyltaurine (NAT) as a biomarker of hyperacetatemia. Aim: Acetate is an important metabolite in metabolic fluxes. Its presence in biological entities originates from both exogenous inputs and endogenous metabolism. Because the change in blood acetate level has been associated with both beneficial and adverse health outcomes, blood acetate analysis has been used to monitor the systemic status of acetate turnover. Methods: The present study examined the use of urinary N-acetyltaurine (NAT) as a marker to reflect the hyperacetatemic status of mice from exogenous inputs and endogenous metabolism, including triacetin dosing, ethanol dosing, and streptozotocin-induced diabetes.  Results: The results showed that triacetin dosing increased serum acetate and urinary NAT but not other N-acetylated amino acids in urine. The co-occurrences of increased serum acetate and elevated urinary NAT were also observed in both ethanol dosing and streptozotocin-induced diabetes. Furthermore, the renal cortex was determined as an active site for NAT synthesis. Conclusions: Overall, urinary NAT behaved as an effective marker of hyperacetatemia in three experimental mouse models, warranting further investigation into its application in humans. W5122 researchers in Minnesota (Chen) examined the profiles of tyrosine fermentation in production animals and humans. Aim: Unabsorbed aromatic amino acids (AAAs), including tyrosine (Tyr), phenylalanine (Phe), and tryptophan (Trp), are the substrates of microbial fermentation in the digestive tract.  Due to the resistance of their aromatic rings to structural degradation, microbial metabolism of AAAs mainly occurs to their alanine moiety through individual or combinatorial reactions, generating a cluster of functional metabolites in humans and production animals with positive or negative effects on health and the environment. In the case of Tyr, the most abundant AAA in vivo, its microbial fermentation mainly bifurcates into the formation of 4-hydroxyphenylpropionic acids (HPPA), a health-promoting compound, and 4-hydroxyphenylacetic acids (HPAA), which is associated with adverse health events. Moreover, HPAA is the direct precursor of p-cresol, a foul-smell environmental hazard. Therefore, understanding the similarities and differences between interspecies in microbial AAA metabolism could facilitate the development of respective modulation approaches for the well-being of health and the environment. Methods: In this study, microbial Tyr metabolites in human and pig feces, broiler excreta, and cow ruminal digesta were profiled by the liquid chromatography-mass spectrometry-based quantitative analysis and multivariate modeling. Results: The results showed that both pigs and broilers predominantly favored the HPAA pathway, with pigs exhibiting significantly higher p-cresol levels compared to broilers, suggesting differential capacities for HPAA conversion to p-cresol.  In contrast, cows and humans displayed a more balanced utilization of both HPPA and HPAA pathways, with humans exhibiting lower overall tyrosine microbial fermentation than the other species. Conclusions: Despite clear species-specific preferences in tyrosine microbial fermentation pathways, notable individual variations were also evident. Therefore, further investigations into the underlying mechanisms, such as enzyme activities, and strategies to mitigate p-cresol production in the pig industry are warranted to alleviate environmental hazards.   Objective 4: Determine how food processing influences chemical composition to affect human health. W5122 researchers in New Mexico (Delgado) worked on optimizing the moisture content and conditioning time in a laboratory-scale flour mill using response surface methodology as a means of increasing flour yield. A central composite experimental design (CCD) using three types of wheat with different hardness was used. Water content and tempering time were evaluated. The results showed an assertiveness of 98.95% and 98.30%, respectively, for yield and ash index; for semi-hard wheat of 99.22% and 99.62% for yield and ash index; and the hard wheat yield of 92.59% of assertiveness, and ash index with assertiveness of 93.54%. These results demonstrate that the optimization of this process could be a useful tool for millers to achieve better yields and quality associated with these variables. W5122 researchers in Colorado (Weir) developed a tempeh (fermented soybean product) that incorporated varying amounts of mealworms. Nutritional, food safety, and finally iron bioavaiability were assessed to determine their potential as a food product. We determined that the insect-based tempeh had similar digestability to the soybean only product, higher protein, and increased iron bioavailability. W5122 researchers in Kentucky (Fan) initiated a study that aims to develop an effective enzymatic method to hydrolyze collagen into low-molecular-weight collagen peptides from the skin of Carp, a fish native to Asia that was introduced to the U.S. in the 1970s to control aquatic vegetation in freshwater environments. Carp have become a significant threat to indigenous species and U.S. waterways, including Kentucky waters, now constituting up to 90% of the fish populations in certain backwaters of the Mississippi River, necessitating continuous population suppression. Unlike many other invasive species, carp can be processed for human consumption, despite not being widely consumed in the U.S. Carp are exceptionally high in protein, primarily myofibrillar proteins and collagen, with collagen comprising ~ 70% of the dry weight of fish skin. The enzymatic approach (pepsin and papain) being developed can achieve a high yield and purity of collagen extraction and peptide preparation from carp. W5122 researchers in Illinois (Helferich) continued to investigate on repeated frying of food such as potatoes, fish, and chicken can alter the oil to product thermally abused frying oil (TAFO) and pan-frying bacon alters the lipid and can have negative impact on breast cancer progression and metastasis.  These products are commonly consumed, and we have demonstrated that these products enhance late-stage breast cancer metastasis.  Once they understand the process for producing these lipids that enhance metastasis, they can develop strategies to alter the processing to reduce the impact of these products to breast cancer survivors. W5122 researchers in Hawaii (Nerurkar) initiated a study to understand the impact of natural fermentation on health beneficial bacteria and metabolites in local foods that can positively impact chronic diseases such as type 2 diabetes. Several local fermented foods are under study. Recent results indicate that natural fermentation of poi significantly increases resistant starches, mineral and health beneficial metabolites. Second goal is to explore approaches to biofortification of tropical functional foods to increase bioactive components. W5122 researchers in Minnesota (Chen) conducted a chemometric survey on whole stillages and distillers dried grains with solubles (DDGS) from biofuel production. Aim: As a staple feed ingredient for livestock and poultry production, the nutrient profile of DDGS is well documented.  However, the profile of intermediate metabolites and non-ethanol chemical compounds produced during fermentation, distillation, and other processing steps in DDGS production has not been examined extensively. Methods: In the current study, whole stillage and DDGS samples were collected from 10 biofuel plants in eight states of midwestern United States and analyzed for nutrient composition as well as chemometric analysis using liquid chromatography-mass spectrometry (LC-MS) and multivariate analysis. Results: The compositional profiles of these samples, including protein, lipid, fiber, and ash contents, were within the expected ranges of values previously reported in the literature. The LC-MS analysis of DDGS samples and whole stillage supernatants identified proline, alanine, asparagine, glutamic acid, and glycine as the most abundant free amino acids (FAA), which was likely due to their high abundance in corn protein. The analysis also identified lactic acid and acetic acids as the most abundant organic acids, as well as the presence of diverse aldehydes and polyamines with highly variable concentrations, which were consistent with their roles as intermediate and fermentation derived metabolites. Interestingly, the principal components analysis-based multivariate modeling revealed the clustering of DDGS and whole stillage samples based on two processing platforms that utilize different amounts of enzymes and heat. This processing-based separation was mainly driven by the differences in multiple essential FAA and other metabolites, including ethanolamine, putrescine, and pentanal. Conclusions: The chemometric profiles of whole stillages and DDGS were defined in this study. Considering the nutritional and biochemical properties of these metabolites, our observations warrant further investigations on the roles of processing conditions in the formation of these functional molecules as well as the nutritional significance of these differences in DDGS. W5122 researchers in Minnesota (Chen) examined the disposition of deoxynivalenol (DON) in nursery and grow-finish pigs under sulfonation-based mitigation treatments. Aim: Deoxynivalenol (DON) is a highly reactive epoxy-sesquiterpenoid mycotoxin commonly present in cereal feed ingredients. Dietary DON contamination negatively affects feed intake, growth, and health status in all stages of swine production. Both in vivo biotransformation, including somatic xenobiotic metabolism and microbial metabolism, and ex vivo chemical mitigation reactions, such as bisulfite-based sulfonation, have been shown to reduce the reactivity and bioavailability of DON and alleviate its toxicity in pigs.  However, whether age and growth could affect DON metabolism and chemical mitigation in pigs has not been examined previously. Methods: In two feeding trials, 48 nursery pigs and 60 grow-finish pigs, respectively, were fed DON-contaminated feeds with or without bisulfite agents. DON and its mitigation products in feeds, as well as their metabolites in excreta samples (feces and urine), were determined by liquid chromatography-mass spectrometry-based metabolomic analysis. Results: The results showed the abundant presence of DON glucuronides in urine and the absence of free DON in feces, indicating extensive absorption and metabolism of DON occurred in both nursery and grow-finish pigs. Nevertheless, the presence of free DON in urine and de-epoxy deoxynivalenol (DOM) in feces only occurred in nursery pigs, while grow-finish pigs excreted more DOM glucuronides in urine than nursery pigs. Bisulfite additives effectively and dose-dependently decreased DON in pig feeds by forming DON sulfonates (DON-S), including DON-S2 and DON-S3. These DON-S were further enriched and concentrated in feces by the formation of DON-S1 and the increase of DON-S2, potentially through the reactions in the digestive system. In addition, bisulfite additives in feed decreased the urinary excretion of DON and its glucuronides in both nursery and grow-finish pigs, but only increased the fecal excretion of DOM in nursey pigs. Conclusions: Overall, compared to nursery pigs, grow-finish pigs might be more efficient in the microbial conversion of DON to DOM, DOM absorption, and somatic production of their glucuronides, which potentially contribute to their differences in DON disposition after bisulfite mitigation treatments.   Grants awards to W5122 members during 2023-24 reporting period (new and ongoing):  W5122 members and their labs were supported by 53 grants from federal agencies, private foundation, industry collaborations, and institutional investments totaling well over $20M during the 2023-24 periodi to study effects of bioactive nutrients on cancer, diabetes, metabolic and gut health, and cardiovascular risk). Major awards from this reporting period are listed below. <table width="0"> <tbody> <tr> <td width="122"> W5122 member </td> <td width="93"> Year </td> <td width="176"> Project Title </td> <td width="121"> Funding Agency </td> <td width="117"> US Dollars (approx.) </td> </tr> <tr> <td rowspan="2" width="122"> Ock Chun (University of Connecticut) </td> <td width="93"> 2025-2029 </td> <td width="176"> Blackcurrants Mitigate Postmenopausal Bone Loss through Gut Microbiota-Bone Axis </td> <td width="121"> USDA-AFRI </td> <td width="117"> $650,000 </td> </tr> <tr> <td width="93"> 2024-2027 </td> <td width="176"> Colon cancer protection derived from prunes.  </td> <td width="121"> National Research Foundation of Korea </td> <td width="117"> ~$200,000 US </td> </tr> <tr> <td rowspan="3" width="122"> Mohit Verma (Purdue University) </td> <td width="93"> 2023-2025 </td> <td width="176"> A universal field-deployable test for measuring and predicting the spread of SARS-CoV-2 in any host species </td> <td width="121"> United States Department of Agriculture Animal and Plant Health Inspection Services </td> <td width="117"> $2,729,261 </td> </tr> <tr> <td width="93"> 2023-2024 </td> <td width="176"> Testbeds for microbial source tracking using microfluidic paper-based analytical devices </td> <td width="121"> Center for Produce Safety Grants Program </td> <td width="117"> $394,516 </td> </tr> <tr> <td width="93"> 2024-2025 </td> <td width="176"> Raman and QCL MIDIR Spectroscopy as a process analytical technology (PAT) tool for Adeno associated viral vectors (AAV) and monoclonal antibodies (mAbs) downstream processes </td> <td width="121"> Eli Lilly and Company </td> <td width="117"> $85,000 </td> </tr> <tr> <td width="122"> Mohit Verma (Purdue University) </td> <td width="93"> 2022-2024 </td> <td width="176"> Point-of-care detection of African swine fever virus: a paper-based device for molecular diagnostics </td> <td width="121"> joint National Animal Health Laboratory Network and National Animal Disease Preparedness and Response Programs in Indiana Agriculture and Rural Communities </td> <td width="117"> $1,000,000 </td> </tr> <tr> <td width="122"> Mohit Verma (Purdue University) </td> <td width="93"> 2021-2024 </td> <td width="176"> Field-deployable biosensors for managing animal health </td> <td width="121"> Foundation for Food and Agriculture Research </td> <td width="117"> $715,000 </td> </tr> <tr> <td width="122"> Mohit Verma (Purdue University) </td> <td width="93"> 2023-2024 </td> <td width="176"> Swallowable smart capsule for targeted gastrointestinal microbiome sampling </td> <td width="121"> NIDDK </td> <td width="117"> $185,242 </td> </tr> <tr> <td rowspan="3" width="122"> Maria Marco (University of California-Davis) </td> <td width="93"> 2022-2026 </td> <td width="176"> PIG-PARADIGM: Preventing Infection in the Gut of developing Piglets-and thus Antimicrobial Resistance - by disentAngling the interface of DIet, the host and the Gastrointestinal Microbiome. </td> <td width="121"> Novo Nordisk Foundation </td> <td width="117">   </td> </tr> <tr> <td width="93"> 2021-2023 </td> <td width="176"> The yogurt matrix during digestion: benefits of milk composition and structure </td> <td width="121"> California Dairy Research Foundation </td> <td width="117">   </td> </tr> <tr> <td width="93"> 2024-2025 </td> <td width="176"> Improving intestinal barrier function with fermented dairy foods </td> <td width="121"> California Dairy Research Foundation </td> <td width="117">   </td> </tr> <tr> <td width="122"> Maria Marco (University of California-Davis) </td> <td width="93"> 2024-2028 </td> <td width="176"> Electro-fermentation for improved fermented fruits and vegetables. </td> <td width="121"> USDA NIFA AFRI </td> <td width="117">   </td> </tr> <tr> <td width="122"> Kaustav Majumder (University of Nebraska-Lincoln) </td> <td width="93"> 2022-2027 </td> <td width="176"> Evaluating the Efficacy of Dry Bean-Based Dietary-Glutamyl Peptides for Improvement of Metabolic Syndrome </td> <td width="121"> USDA Hatch Multistate Enhanced Program </td> <td width="117"> $217,472 </td> </tr> <tr> <td width="122"> Kaustav Majumder (University of Nebraska-Lincoln) </td> <td width="93"> 2023-2024 </td> <td width="176"> Alfalfa Seed Utilization for Human Food </td> <td width="121"> Dept of Agriculture-ARS (USDA-ARS-NCAUR)   </td> <td width="117"> $133,441 </td> </tr> <tr> <td width="122"> Kaustav Majumder (University of Nebraska-Lincoln) </td> <td width="93"> 2023-2024 </td> <td width="176"> Development of Plant Protein-Based High-Value and Innovative Food Products from Nebraska Pulses </td> <td width="121"> Specialty Crop Block Grant Program, Nebraska Department of Agriculture </td> <td width="117"> $38,449 </td> </tr> <tr> <td width="122"> Kaustav Majumder (University of Nebraska-Lincoln) </td> <td width="93"> 2023-2024 </td> <td width="176"> Dry Edible Beans as an Efficacious Alternative for the Development of Fortified-Blended Foods for Food-Aid Program </td> <td width="121"> Specialty Crop Block Grant Program, Nebraska Department of Agriculture </td> <td width="117"> $55,767 </td> </tr> <tr> <td width="122"> Kaustav Majumder (University of Nebraska-Lincoln) </td> <td width="93"> 2021-2024 </td> <td width="176"> Elucidating the Health Beneficial Traits of Kernels of Maize Relatives Digested in the Human Gastrointestinal Tract </td> <td width="121"> USDA Agriculture and Food Research Initiative- NIFA   </td> <td width="117"> $500,000 </td> </tr> <tr> <td width="122"> Hongbin Fan (University of Kentucky) </td> <td width="93"> 2024-2026 </td> <td width="176"> Utilizing Collagen of the Invasive Asian Carp, An Underutilized Protein Source </td> <td width="121"> USDA Agriculture and Food Research Initiative- NIFA   </td> <td width="117"> $300,000 </td> </tr> <tr> <td width="122"> Hongbin Fan (University of Kentucky) </td> <td width="93"> 2024-2028 </td> <td width="176"> Acquisition of a Triple Quadrupole LC/MS for Multi-Omic Metabolite, Lipid, and Peptide Analyses </td> <td width="121"> USDA Agriculture and Food Research Initiative- NIFA   </td> <td width="117"> $398,262 </td> </tr> <tr> <td rowspan="5" width="122"> Adam Chicco (Colorado State University) </td> <td width="93"> 2023-2025 </td> <td width="176"> Conditional Fads2-KO mouse for investigating nutri-genetic regulation of cardiometabolic risk </td> <td width="121"> Colorado Agricultural Experimental Station (USDA) </td> <td width="117"> $50,000 </td> </tr> <tr> <td width="93"> 2022-2025 </td> <td width="176"> Evolutionarily conserved variations in menaquinone structure: Functional implications </td> <td width="121"> National Science Foundation  </td> <td width="117"> $528,000 </td> </tr> <tr> <td width="93"> 2024-2027 </td> <td width="176"> Genetic diversity of human heart responses to low-dose radiation </td> <td width="121"> DOE (Co-PI) </td> <td width="117"> $488,456 </td> </tr> <tr> <td width="93"> 2024-2026 </td> <td width="176"> Investigating the Role of Thyroid Hormone in Placental Function </td> <td width="121"> NIH (Co-I) </td> <td width="117"> $415,490 </td> </tr> <tr> <td width="93"> 2024-2027 </td> <td width="176"> Sex-specificity of radiation-induced cardiac injury in a genetically diverse population </td> <td width="121"> NIH (Co-PI) </td> <td width="117"> $200,986 </td> </tr> <tr> <td width="122"> Tiffany Weir (Colorado State University) </td> <td width="93"> 2023-2026 </td> <td width="176"> Diet and microbiome interactions: application in posttraumatic stress disorder (D-MAPS </td> <td width="121"> Immunology, Inflammation, and Infectious Disease (3i) Initiative and the Cumming Foundation </td> <td width="117"> $60,000 </td> </tr> <tr> <td width="122"> Tiffany Weir (Colorado State University) </td> <td width="93"> 2023-2027 </td> <td width="176"> CoSMIC: Colorado State Microbiome Innovation Consortium </td> <td width="121"> TUNE mechanism; CSU VPR </td> <td width="117"> $1,200,000 </td> </tr> <tr> <td width="122"> Tiffany Weir (Colorado State University) </td> <td width="93"> 2023-2025 </td> <td width="176"> Munispore: Examining Bacillus clausii on intestinal function and regularity. </td> <td width="121"> ADM/Deerland Enzymes and Probiotics </td> <td width="117"> $112,000 </td> </tr> <tr> <td width="122"> Tiffany Weir (Colorado State University) </td> <td width="93"> 2023-2025 </td> <td width="176"> Tetrasol: Effects of a Microalgae Extract Dietary Supplement on Gut Health, Anxiety, and Immune Function </td> <td width="121"> Mycrophyt, LLC </td> <td width="117"> $216,000 </td> </tr> <tr> <td width="122"> Tiffany Weir (Colorado State University) </td> <td width="93"> 2023-2024 </td> <td width="176"> Examination of the bi-directional interactions between phytocannabinoids and a human-associated gut microbiota. </td> <td width="121"> Institute for Cannabis Research </td> <td width="117"> $189,000 </td> </tr> <tr> <td width="122"> Tiffany Weir (Colorado State University) </td> <td width="93"> 2019-2024 </td> <td width="176"> Discovery and Biological Signatures of Microbiome-Derived Xanthohumol Metabolites and their Role in Ameliorating Inflammatory Bowel Disease </td> <td width="121"> NIH (Co-I) </td> <td width="117">   </td> </tr> <tr> <td width="122"> Claudia Maier (Oregon State University) </td> <td width="93"> 2024-2025 </td> <td width="176"> Mass spectrometer with electron activated dissociation capability </td> <td width="121"> USDA (Co-I) </td> <td width="117"> $500,000 </td> </tr> <tr> <td width="122"> Claudia Maier (Oregon State University) </td> <td width="93"> 2022-2025 </td> <td width="176"> Single Cell Proteomics </td> <td width="121"> Hewlett Packard/Oregon State University Collaboration Grant </td> <td width="117"> $265,000 </td> </tr> <tr> <td width="122"> Claudia Maier (Oregon State University) </td> <td width="93"> 2023-2025 </td> <td width="176"> Computation-assisted discovery of bioactive minor cannabinoids from hemp (Co-I) </td> <td width="121"> NIH </td> <td width="117"> $400,000 </td> </tr> <tr> <td width="122"> Claudia Maier (Oregon State University) </td> <td width="93"> 2021-2025 </td> <td width="176"> Botanical Dietary Supplements Research Centers (BDSRC) on Botanicals Enhancing Neurological and Functional Resilience in Aging (BENFRA) </td> <td width="121"> NIH </td> <td width="117"> $1,600,000 </td> </tr> <tr> <td width="122"> Pratibha V Nerurkar (University of Hawaii) </td> <td width="93"> 2021-2026 </td> <td width="176"> Empowering Women and Underrepresented Undergraduates with Advanced Technology Research Training in Agriculture and Food Sciences </td> <td width="121"> AFRI-NIFA </td> <td width="117"> $440,367 </td> </tr> <tr> <td rowspan="3" width="122"> Pratibha V Nerurkar (University of Hawaii) </td> <td width="93"> 2018-2024 </td> <td width="176"> Specialty Crops: From Farm to Human Health </td> <td width="121"> USDA- ARS </td> <td width="117"> $80,000 </td> </tr> <tr> <td width="93"> 2021-2024 </td> <td width="176"> Developing an Alliance for Training and Apprenticeship in Climate-Smart Agriculture (DATA-Ag) </td> <td width="121"> USDA-AFRI-AWT Program through UT at Arlington.   </td> <td width="117"> $124,852   </td> </tr> <tr> <td width="93"> 2021 -2024   </td> <td width="176"> Training of Next Generation Workforce for Smart Food Science and Agricultural Technology in the Digital Era (WorkFoS-Ag) </td> <td width="121"> USDA-AFRI   </td> <td width="117"> $500,000 </td> </tr> <tr> <td rowspan="2" width="122"> Efren Delgado (New Mexico State University) </td> <td width="93"> 10/01/2022 – 09/30/2025   </td> <td width="176"> Genetic dissection of Phytophthora capsici resistance in chile pepper using epigenomic and transcriptomic approaches </td> <td width="121"> New Mexico Department of Agriculture (NMDA) - Specialty Crop Grant Program (SCBGP) </td> <td width="117"> $102,562 </td> </tr> <tr> <td width="93"> 2021-2026   </td> <td width="176"> Bioprocessing of Agroindustrial By-products   </td> <td width="121"> Hatch-Proposal- US Department of Agriculture   </td> <td width="117"> $27,500   </td> </tr> <tr> <td width="122"> Tilton (PI) Oregon State University </td> <td width="93"> 2022-2024 </td> <td width="176"> Development of a 3D respiratory co-culture model for assessing toxicity to chemicals from wildfire smoke </td> <td width="121"> Center for Translational Environmental Health Research   </td> <td width="117"> $25,000 </td> </tr> <tr> <td width="122"> Tilton (PI) Oregon State University </td> <td width="93"> 2020-2025 </td> <td width="176"> Linking PAH Exposure to Health Outcomes Using Human Primary In Vitro Respiratory Model </td> <td width="121"> NIH/NIEHS P42 ES016465 </td> <td width="117"> $1,470,000 </td> </tr> <tr> <td width="122"> Tilton (PI) Oregon State University </td> <td width="93"> 2022-2024 </td> <td width="176"> Linking PAH Exposure to Health Outcomes Using Human Primary In Vitro Respiratory Model </td> <td width="121"> NIH/NIEHS P42 ES016465 Supplement </td> <td width="117"> $100,000 </td> </tr> <tr> <td width="122"> Kolluri (PI) Oregon State University </td> <td width="93"> 2021-2024 </td> <td width="176"> Bcl-2 as a target in cancer </td> <td width="121"> NIH/NCI R21CA249627 </td> <td width="117"> $400,000 </td> </tr> <tr> <td width="122"> Kolluri (PI) Oregon State University </td> <td width="93"> 08/01/2020- 6/30/2024 </td> <td width="176"> Processed Food Intake, Metabolomics, and Adiposity </td> <td width="121"> NIH R01 </td> <td width="117">   </td> </tr> <tr> <td width="122"> Kolluri (PI) Oregon State University </td> <td width="93"> 07/2024-06/2025 </td> <td width="176"> Integrated Regional Training Program in Environmental Health Sciences (Marcus and Kolluri – MPI) </td> <td width="121"> NIH </td> <td width="117"> $2,500,000 </td> </tr> <tr> <td width="122"> Kolluri (PI) Oregon State University </td> <td width="93"> 1/1/2024-12/31/2027 </td> <td width="176"> Acquisition of Combustion Elemental Analyzer to Strengthen Agricultural Research at the University of Minnesota </td> <td width="121"> USDA </td> <td width="117"> $500,000 </td> </tr> <tr> <td width="122"> Chi Chen (Co-I); University of Minnesota </td> <td width="93"> 3/1/2023-2/28/2025 </td> <td width="176"> Advancing Biorefinery of Camelina and Pennycress Meal for Valuable Products </td> <td width="121"> Minnesota Forever Green Initiative </td> <td width="117">   </td> </tr> <tr> <td width="122"> Chi Chen (Co-I); University of Minnesota </td> <td width="93"> 2020-2024 </td> <td width="176"> Processed Food Intake, Metabolomics, and Adiposity </td> <td width="121"> NIH </td> <td width="117">   </td> </tr> <tr> <td width="122"> Chi Chen (Co-PI); University of Minnesota </td> <td width="93"> 2023-2027 </td> <td width="176"> Lysine requirements that maximize reproductive performance in pregnant sows </td> <td width="121"> USDA </td> <td width="117"> $500,000 </td> </tr> <tr> <td width="122"> Chi Chen (Co-I); University of Minnesota </td> <td width="93"> 2023-2025 </td> <td width="176"> By beneficially altering microbiome, yogurt (the whole food) may be more beneficial to mental health than non-dairy probiotic supplement </td> <td width="121"> National Dairy Council </td> <td width="117">   </td> </tr> <tr> <td width="122"> Jacques Izard (University of Nebraska) </td> <td width="93"> 2018-2023 </td> <td width="176"> Digestive Tract Microbiome in Healthy Term Infants receiving Mothers-Own Breast Milk or Cows Milk-Based Infant Formulas </td> <td width="121"> Mead Johnson Nutrition </td> <td width="117">   </td> </tr> <tr> <td width="122"> Jacques Izard (University of Nebraska) (Co-investigator; PI: Dr. Kerry Ivey) </td> <td width="93"> 2023-2025 </td> <td width="176"> By beneficially altering microbiome, yogurt (the whole food) may be more beneficial to mental health than non-dairy probiotic supplements </td> <td width="121"> National Dairy Council </td> <td width="117"> $303,994 </td> </tr> <tr> <td width="122"> Nick Bello  (Rutgers University; PI) </td> <td width="93"> 2019-2024 </td> <td width="176"> The Role of Lateral Hypothalamus Orexin Glucose-Inhibited Neurons in Binge- Eating Disorder </td> <td width="121"> DOD </td> <td width="117"> $1,019,612 </td> </tr> </tbody> </table>

Publications

Publications: There were 77 new publications by W5122 members in 2023-2024 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 W5122 group members in boldfaced text.  <ol> <li>Briana M. Nosal, Staci Thornton, Alexey Melnik, Ali Lofti, Manije Darooghegi Mofrad, Alexander Aksenov, Elaine Choung-Hee Lee and Ock K. Chun. Blackcurrant anthocyanins attenuate estrogen deficiency-induced bone loss through modulating microbial-derived short-chain carboxylic acids and phytoestrogen metabolites in peri- and early postmenopausal women. Metabolites 2024, 14, 541. <a href="https://doi.org/10.3390/metabo14100541">https://doi.org/10.3390/metabo14100541</a></li> <li>Mao Q, Shi X, Ma Y, Lu Y, Chen C. Characterization of Urinary N-Acetyltaurine as a Biomarker of Hyperacetatemia in Mice. Metabolites. 14: 322 (2024). <a href="https://doi.org/10.3390/metabo14060322">https://doi.org/10.3390/metabo14060322</a></li> </ol> <ol> <li>Heidari F, Øverland M, Hansen JØ, Mydland LT, Urriola PE, Chen C, Shurson GC, Hu B. Enhancing the nutritional value of canola meal through solid culture with Pleurotus ostreatus. Animal Feed Science and Technology. 309: 115893 (2024) <a href="https://doi.org/10.1016/j.anifeedsci.2024.115893">https://doi.org/10.1016/j.anifeedsci.2024.115893</a></li> <li>Ravelo AD, Ferm P, Guo Y, Omontese BO, Morley PS, Chen C, Noyes NR, Caixeta LS. Using a multi-omics approach to explore potential associations with rumen content and serum of cows with different milk production levels based on genomic predicted transmitting ability for milk and phenotypic milk production. PloS one. 19: e0305674 (2024) doi: <a href="https://doi.org/10.1371%2Fjournal.pone.0305674">10.1371/journal.pone.0305674</a></li> <li>Trudeau M, Mosher W, Tran H, de Rodas B, Karnezos TP, Urriola PE, Gomez A, Saqui-Salces M, Chen C, Shurson GC. Growth Performance, Metabolomics, and Microbiome Responses of Weaned Pigs Fed Diets Containing Growth-Promoting Antibiotics and Various Feed Additives. Animals. 14: 60 (2024) DOI: <a href="https://doi.org/10.3390/ani14010060">10.3390/ani14010060</a></li> <li>Onarman Umu ÖC, Mydland LT, Chen C, de Nanclares MP, Shurson GC, Urriola PE, Sørum H, Øverland M. Integrated multi-omics approach reveals novel associations in the rapeseed diet–microbiota–host axis in pigs. ISME communications. 4: ycae061 (2024) DOI: <a href="https://doi.org/10.1093/ismeco/ycae061">10.1093/ismeco/ycae061 </a></li> <li>Yang J, Gourley GR, Gilbertsen A, Chen C, Wang L, Smith K, Namenwirth M, Yang L. High Glucose Levels Promote Switch to Synthetic Vascular Smooth Muscle Cells via Lactate/GPR81. Cells 13: 236 (2024), <a href="https://doi.org/10.3390/cells13030236">https://doi.org/10.3390/cells13030236</a></li> <li>Duddeck KA, Petersen TE, Adkins HJ, Smith AH, Hernandez S, Wenner SJ, Yao D, Chen C, Li W, Fregulia P, Larsen A, Jang YD. Dose-Dependent Effects of Supplementing a Two-Strain Bacillus subtilis Probiotic on Growth Performance, Blood Parameters, Fecal Metabolites, and Microbiome in Nursery Pigs. Animals. 14: 109 (2024) DOI: <a href="https://doi.org/10.3390/ani14010109">10.3390/ani14010109</a></li> </ol> <ol start="9"> <li>Quintero Quiroz, J, Velazquez, V, Torres, JD, Ciro, G, Delgado, E, Rojas, J. 2024. Effect of the structural modification of plant proteins as microencapsulating agents of bioactive compounds from annatto seeds (Bixa Orellana L.). Foods. 13(15), 2345; https://doi.org/10.3390/foods13152345.</li> <li>Paśko P, Galanty A, Dymerski T, Kim YM, Park YS, Cabrales-Arellano P, Velazquez Martinez V, Delgado E, Gralak M, Deutsch J, Barasch D, Nemirovski A, Gorinstein S. 2024. Physicochemical and Volatile Compounds Analysis of Fruit Wines Fermented with Saccharomyces cerevisiae: FTIR and Microscopy Study with a Focus on Anti-inflammatory Potential. International Journal of Molecular Sciences 25, 5627. https://doi.org/10.3390/ijms25115627.</li> <li>Martínez Ávalos, JF, Gamero Barraza, JI. Delgado, E, Guerra Rosas, MI, Gómez Aldapa, CA. Medrano Roldán, H. Reyes Jáquez, D. 2024. Study of molecular dynamic interactions during the optimized extrusion processing of corn (Zea mays) and substandard bean (Phaseolus vulgaris). Food Chemistry Advances 4, 100723. https://doi.org/10.1016/j.focha.2024.100723.</li> <li>Gamero-Barraza, JI, Pámanes-Carrasco, GA, Delgado, E, Cabrales-Arellano, CP, Medrano-Roldán, H, Gallegos-Ibáñez, D, Wedwitschka, H, Reyes Jáquez, D. 2024. Computational modelling of extrusion process temperatures on the interactions between black soldier fly larvae protein and corn flour starch. Food Chemistry: Molecular Science 8, 2024. https://doi.org/10.1016/j.fochms.2024.100202.</li> <li>Paśko P, Galanty A, Ramos-Zambrano E, Martinez Ayala, AL, Delgado E, Gdula – Argasińska J, Zagrodzki P, Podsiadły P, Deutsch J, Gorinstein S. 2024. Pseudocereal oils, authenticated by Fourier transform infrared spectroscopy, and their chemopreventive properties. Plant Foods for Human Nutrition.</li> <li>Gaucin Gutiérrez, S.C., Rojas-Contreras, J.A., Zazueta-Álvarez, D.E., Delgado, E., Vázquez Ortega, P.G., Medrano Roldán, H., Reyes Jáquez, D. 2024. Exploration of In Vitro Voltage Production by a Consortium of Chemolithotrophic Microorganisms Using Galena (PbS) as a Sulphur Source. Clean Technologies, 6(1), 62-67. https://doi.org/10.3390/cleantechnol6010005.</li> <li>Chloe Christensen, Car Reen Kok, Cheryl L Harris, Nancy Moore, Jennifer L Wampler, Weihong, Zhuang, Steven S Wu, Robert Hutkins, Jacques Izard, Jennifer M. Auchtung. Microbiota, metabolic profiles and immune biomarkers in infants receiving formula with added bovine milk fat globule membrane: a randomized, controlled trial, Frontiers Nutrition (2024) 11:1465174</li> <li>Nancy D. Turner, Tiffany L. Weir, and Jacques Izard. Intersection of Diet, Intestinal Microbiota and Their Metabolites on Cancer Prevention. Frontiers in Nutrition (2024) 10:1358428</li> <li>Road map Contributors (Jacques Izard as a contributor to all 3 technical themes “Health and Medicine” “Food and Nutrition”, and “Environmental Control and Life Support”); Engineering Biology Space Health, An Innovative Research Road Map; Engineering Biology Research Consortium (EBRC) Publisher (2024)</li> <li>Arghya Mukherjee, Samuel Breselge, Eirini Dimidi, Maria L Marco, and Paul D Cotter. 2023. Fermented foods and gastrointestinal health: underlying mechanisms. Nature Reviews Gastroenterology & Hepatology. 21:248–266.</li> <li>Lynne V McFarland, Gail Hecht, Mary E Sanders, Debra A Goff, Ellie J C Goldstein, Colin Hill, Stuart Johnson, Maryam R Kashi, Ravina Kullar, Maria L Marco, Daniel J Merenstein, Mathieu Millette, Geoffrey A Preidis, Eamonn M Quigley, Gregor Reid, Seppo Salminen, Jason C Sniffen, Harry Sokol, Hania Szajewska, Daniel J Tancredi, Kristin Woolard. 2023. Recommendations to improve quality of probiotic systematic reviews with meta-analyses: Developed by expert Delphi consensus. JAMA Network Open. 6(12):e2346872.</li> <li>Maany Ramanan, Glen Fox, and Maria L. Marco. 2024. Beer for live microbe delivery. Journal of Functional Foods. 113:105987.</li> <li>Mateus L.P. Lemos, Guilherme M. Leite, Liliane P. Santana, Nelquides B. Vianaa, Wydemberg J. Araújo, Wannes Van Beeck, Maria L. Marco, Anderson M. Zanine, Edson M. Santos, Celso J.B. Oliveira. 2024. Bacterial community dynamics of spineless cactus silage during fermentation and aerobic stability. Bioresource Technology Reports. 25:101762</li> <li>Jee-Yon Lee, Connor R. Tiffany, Scott P. Mahan, Matthew Kellom, Andrew W.L. Rogers, Henry Nguyen, Eric T. Stevens, Hugo L.P. Masson, Kohei Yamazaki, Maria L. Marco, Emiley A. Eloe-Fadrosh, Peter J. Turnbaugh, and Andreas J. Baumler. 2024. High fat intake sustains sorbitol intolerance after antibiotic-mediated clostridia depletion from the gut microbiota. Cell. 87(5):1191-120</li> <li>Glory Bui, Cristina Torres-Fuentes, Matteo M Pusceddu, Mélanie G Gareau, and Maria L Marco. 2024. Milk and Lacticaseibacillus casei BL23 effects on intestinal responses in a murine model of colitis. American Journal of Physiology and Gastrointestinal Liver Physiology. 326(6):G659-G675..</li> <li>Lei Wei, Dana Wong, Tina Jeoh, Maria L. Marco. 2024. Intestinal delivery of encapsulated bacteriocin peptides in cross-linked alginate microcapsules. Food Research International. 118:114473.</li> <li>Hisham Hussan, Mohamed R. Aly, Victoria Lyo, Amy Webb, Maciej Pietrzak, Jiangjiang Zhu, Fouad Choueiry, Hong Li, Bethany P. Cummings, Maria L. Marco, Valentina Medici, and Steven K. Clinton. 2024. Concentrations of fecal secondary bile acids and their metabolizing microbial enzymes: a pilot study. Obesity Surgery. 34: 3420–3433.</li> <li>Sabina Fijan, Polona Fijan, Lei Wei, and Maria L. Marco. 2024. Health benefits of kimchi, sauerkraut and other fermented foods of the genus Brassica. Applied Microbiology. 4(3), 1165-1176.</li> <li>Colvin V, Bramer LM, Rivera BN, Pennington JM, Waters KM, Tilton SC. 2024. Modeling PAH mixture interactions in a human in vitro organotypic respiratory model. Int. J. Mol. Sci. 25(8), 4326. doi.org/10.3390/ijms25084326. PMCID: PMC11050152.</li> <li>Valdez R, Rivera BN, Chang Y, Pennington JM, Fischer KA, Lohr CV, Tilton SC. 2024. Assessing susceptibility for polycyclic aromatic hydrocarbon toxicity in an in vitro 3D respiratory model for asthma. Frontiers in Toxicology, Special Issue “Linking Environmental Exposure to Toxicants and Chronic Disease”. 6:1287863. doi.org/10.3389/ftox.2024.1287863. PMCID: PMCID11066177.</li> <li>Maier MLV, Siddens LK, Pennington JM, Uesugi SL, Labut E, Vertel EA, Anderson KA, Tidwell LG, Tilton SC, Ognibene TJ, Turteltaub KW, Smith JN, Williams DE. 2023. Impact of Phenanthrene Co-Administration on the Toxicokinetics of Benzo[a]pyrene in Humans. UPLC-Accelerator Mass Spectrometry Following Oral Microdosing. Chemico-Biological Interactions. 382:110608. doi: 10.1016/j.cbi.2023.110608. PMID: 37369263.</li> <li>Kim, T., Esmaili, E., Athalye, S.M., Matos, T., Hosseini, M., Verma, M.S., and Ardekani, A.M.* (2024) Acoustofluidic device focusing viral nanoparticles for Raman microscopy. Sensors and Actuators B: Chemical 136438 DOI: 10.1016/j.snb.2024.136438</li> <li>Wang, J., Kaur, S., Kayabasi, A., Ranjbaran, M., Rath, I., Benschikovski, I., Raut, B., Ra, K., Rafiq, N., Verma, M.S.* (2024) A portable, easy-to-use paper-based biosensor for rapid in-field detection of fecal contamination on fresh produce farms Biosensors and Bioelectronics: 116374. DOI: 10.1016/j.bios.2024.116374</li> <li>Kamel, M.S., Davidson, J.L., Verma, M.S.* (2024) Strategies for Bovine Respiratory Disease (BRD) Diagnosis and Prognosis: A Comprehensive Overview Animals: 14(4): 627. DOI: 10.3390/ani14040627</li> <li>Wang, J.,§ Ranjbaran, M.,§ Verma, M.S.* (2024) Bacteroidales as a Fecal Contamination Indicator in Fresh Produce Industry: A Baseline Measurement. Journal of Environmental Management: 351:119641 DOI: 10.1016/j.jenvman.2023.119641</li> <li>Marney LC, Choi J, Alcazar Magana A, Yang L, Techen N, Alam MN, Brandes M, Soumyanath A, Stevens JF, Maier CS. Liquid chromatography-mass spectrometry quantification of phytochemicals in Withania somnifera using data-dependent acquisition, multiple-reaction-monitoring, and parallel-reaction-monitoring with an inclusion list. Front Chem. 2024 Jul 17;12:1373535. doi:10.3389/fchem.2024.1373535. PMID: 39100918; PMCID: PMC11294917.</li> <li>Rowe K, Gray NE, Zweig JA, Law A, Techen N, Maier CS, Soumyanath A, Kretzschmar D. Centella asiatica and its caffeoylquinic acid and triterpene constituents increase dendritic arborization of mouse primary hippocampal neurons and improve age-related locomotion deficits in Drosophila. Front Aging. 2024 Jul 11;5:1374905. doi: 10.3389/fragi.2024.1374905. PMID: 39055970; PMCID: PMC11269084.</li> <li>Gray NE, Hack W, Brandes MS, Zweig JA, Yang L, Marney L, Choi J, Magana AA, Cerruti N, McFerrin J, Koike S, Nguyen T, Raber J, Quinn JF, Maier CS, Soumyanath A. Amelioration of age-related cognitive decline and anxiety in mice by Centella asiatica extract varies by sex, dose and mode of administration. Front Aging. 2024 May 6;5:1357922. doi: 10.3389/fragi.2024.1357922. PMID: 38770167; PMCID: PMC11102990.</li> <li>Alcázar Magaña A, Vaswani A, Brown KS, Jiang Y, Alam MN, Caruso M, Lak P, Cheong P, Gray NE, Quinn JF, Soumyanath A, Stevens JF, Maier CS. Integrating High-Resolution Mass Spectral Data, Bioassays and Computational Models to Annotate Bioactives in Botanical Extracts: Case Study Analysis of asiatica Extract Associates Dicaffeoylquinic Acids with Protection against Amyloid-β Toxicity. Molecules. 2024 Feb 13;29(4):838. doi: 10.3390/molecules29040838.</li> <li>Jamieson PE, Smart EB, Bouranis JA, Choi J, Danczak RE, Wong CP, Paraiso IL, Maier CS, Ho E, Sharpton TJ, Metz TO, Bradley R, Stevens JF. Gut enterotype-dependent modulation of gut microbiota and their metabolism in response to xanthohumol supplementation in healthy adults. Gut Microbes. 2024 Jan-Dec;16(1):2315633. doi: 10.1080/19490976.2024.2315633. Epub 2024 Feb 15. PMID:38358253; PMCID: PMC10878022.</li> <li>Yang L, Marney L, Magana AA, Choi J, Wright K, Mcferrin J, Gray NE, Soumyanath A, Stevens JF, Maier CS. Quantification of Caffeoylquinic Acids and Triterpenes as Targeted Bioactive Compounds of Centella asiatica in Extracts and Formulations by Liquid Chromatography Mass Spectrometry. J Chromatogr Open. 2023 Nov 27;4:100091. doi: 10.1016/j.jcoa.2023.100091. Epub 2023 Jul 8. PMID: 37789901; PMCID: PMC10544816.</li> <li>Holvoet H, Long DM, Yang L, Choi J, Marney L, Poeck B, Maier CS, Soumyanath A, Kretzschmar D, Strauss R. Chlorogenic Acids, Acting via Calcineurin, Are the Main Compounds in Centella asiatica Extracts That Mediate Resilience to Chronic Stress in Drosophila melanogaster. Nutrients. 2023 Sep 16;15(18):4016. doi: 10.3390/nu15184016. PMID: 37764799; PMCID: PMC10537055.</li> <li>Newman NK, Zhang Y, Padiadpu J, Miranda CL, Magana AA, Wong CP, Hioki KA, Pederson JW, Li Z, Gurung M, Bruce AM, Brown K, Bobe G, Sharpton TJ, Shulzhenko N, Maier CS, Stevens JF, Gombart AF, Morgun A. Reducing gut microbiome-driven adipose tissue inflammation alleviates metabolic syndrome. 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Impact Statements

W5122 researchers in Nebraska (Izard) revealed insights into the potential benefits of supplementing infant formula with MFGM to more closely mimic the effects of breast milk on gut health and early immune development, supporting the formulation of improved infant nutrition products that could aid infants who cannot be breastfed, potentially influencing their long-term health outcomes.
W5122 researchers in Nebraska (Majumder) provided the first comprehensive investigation into the role of dietary γ-glutamyl peptides in mitigating cardio-metabolic disorders, revealing complex interactions with the gut microbiota and vascular function a potential mechanisms of action.
W5122 researchers in Indiana (Verma) developed a high-resolution biogeographical map of the gastrointestinal microbiome of pigs as model for studying diet impacts on the health of monogastric mammals (including humans).
W5122 researchers in Hawaii (Nerurkar) provided scientific evidence and increasing bioactive compounds and minerals through biofortification that may increase consumption of fermented foods and prevent/lower incidences of chronic diseases and metabolic syndrome.
W5122 researchers in Colorado (Weir) established the safety and tolerability of three novel food ingredients/supplements.
W5122 researchers in Colorado (Weir) identified potential dietary strategies for mitigating gastrointestinal symptoms.
W5122 researchers in Colorado (Weir) developed an experimental workflow for determining the role of gut microbiota in response/non-response to dietary interventions.
W5122 researchers in Illinois (Helferich) generated results that provide a basis for clinical trials testing impact of cooking of commonly consumed foods that impact metastatic tumor development and treatments, and inform the broader public of the health consequences of consuming deep fried foods and pan fried bacon
W5122 researchers in Minnesota (Chen) identified a novel metabolite biomarker of hyperacetatemia, a pathological status of metabolic disorders and disruptions. We determined the metabolic fates of tyrosine in multiple species and deoxynivalenol in pigs. These results could be used to guide the metabolism analysis in nutrition, toxicology, and industrial applications. All these research activities provided training opportunities for graduate students, undergraduate, postdoc, and visiting scholars.
W5122 researchers in California (Marco) is discovering ways to improve the production of fermented foods for enhanced sensory properties, shelf-life, and health benefits.
W5122 researchers in California (Marco) are learning how background diets can alter how dietary live microbes, such as those used as probiotics or in foods, affect the gut microbiome and intestinal environment, and ultimately impact human health.
W5122 researchers in Oregon (Tilton) show that combined exposure to dietary carcinogens can markedly alter metabolism and toxicokinetics of chemicals in human plasma, as well as lead to an underestimation of risk based on standard modeling of chemical mixture interactions assuming additivity.
W5122 researchers in Oregon (Tilton) completed the first studies to evaluate the role of combined environmental factors associated with inflammation from pre-existing disease and PAH exposure on pulmonary toxicity in a physiologically relevant human in vitro model.
W5122 researchers in Oregon (Maier) provided mechanistic insights into the efficacy and safety of the highly popular dietary supplements, ashwagandha and gotu kola, used as a remedy for reducing stress and enhancing resilience to aging associated decline in cognitive and locomotion function.
W5122 researchers in Oregon (Kolluri) identified small molecule “Bcl-2 functional converters” compounds that are envisioned to work as targeted cancer therapeutics to inhibit overexpression of Bcl-2 signaling in active tumors.
W5122 researchers in Connecticut (Chun) found that blackcurrant (BC) consumption reduces postmenopausal bone loss via enhancing the production of SCCAs and phytoestrogen metabolites in the gut, which can be translated into dietary recommendations for adult women.
W5122 researchers in Colorado (Chicco) generated a novel model mode for experimental validation and investigation of the nutri-genetic interactions between the FADS2 gene and dietary polyunsaturated fatty acid intake on cardiometabolic risk suggested by human epidemiological studies.
W5122 researchers in New Mexico (Delgado) developed simulations and process optimization models for optimizing and predicting yield and ash index, an important tool for millers to predict the potential yield in a laboratory mill.
W5122 researchers in Kentucky (Fan) demonstrated that pepsin and papain were proved to be effective in extracting collagen and hydrolyzing it into collagen peptides from carp, potentially making productive use of this invasive species that can align with local population control efforts.
W5122 researchers in New Jersey (Bello) determined that kratom alkaloids influence cardiovascular parameters, but not weight gain, in a mouse model of obesity.