Brief Summary of Minutes of Annual Meeting

Tuesday - Wednesday, September 9-10, 2025:

Participants attended the Linus Pauling Institute’s 13th biennial Diet and Optimum Health Conference will focus on catalyzing new research at the frontiers of precision nutrition.  The conference program explored perspectives, innovations, and new ideas shaping precision nutrition research and healthspan. Featured topics include diet and dietary supplements, nutrition and the microbiome, inflammation and immunity, and cutting-edge data technologies.

Thursday, September 11, 2025:

9:05 – 9:20 AM – Dr. Shawn Donkin, College of Agricultural Sciences Associate Dean of Research and Associate Director of the Oregon Agricultural Research Station provided opening remarks and a presentation about ongoing research initiatives and funding perspectives from the College of Agricultural Sciences at Oregon State University. 

9:25 – 9:55 AM - Dr. Pascale Jean, National Program Leader, USDA Institute of Food Safety and Nutrition presented a comprehensive overview of writing successful USDA NIFA grant applications, emphasizing the importance of understanding guidelines, clear communication, and proper formatting. She highlighted key elements such as focusing objectives, addressing evaluation criteria, and building timelines for both projects and submissions. Pascale also discussed common criticisms and provided tips for improving proposal success rates, including submitting early and utilizing visual aids. She addressed specific requirements for USDA NIFA applications, such as letters of support and attachments, and encouraged faculty to take advantage of available resources and support from their institutions.  Recommended faculty contact program directors for guidance on proposal fit and process questions and prepare 1-page proposal summaries for initial program director discussions.

10:00 – 10:30 AM - Liz Etherington, College of Agricultural Sciences Director of Sponsored Programs Servies, Orgon State University, presented on successful USDA NIFA and NSF grant writing strategies, covering key requirements and best practices for proposal submissions.  Primary recommendations are to:

• Ensure broader impacts activities are open to all participants and include recruitment plans
• Include budget for broader impacts activities and evaluation
• Frame proposals addressing both basic research and potential applications in the broader impacts section
• Contact administrative research support team if needed
• Use a timeline builder tool for proposal submission planning
• Obtain multiple non-friendly reviews of proposals
• Ensure all proposal requirements are prepared early and follow instructions
• Include specific aims, hypotheses, and contingency plans in proposals
• Highlight innovative components, interdisciplinary aspects, and alignment with agency priorities
• Provide clear, concise, and well-formatted proposals with headers and visual aids
• Include letters of support that are tailored and not cookie-cutter
• Use active voice and simple constructions in proposal writing
• Ensure budget and justification align with project goals and timelin 

10:30 – 11:15 AM – Dr. Courtney Jahn (NSF Program Director for Plant Biotic Interactions), Dr. Kathryn Dickson (NSF Program Director for Physiological Mechanisms and Biomechanics Program), Dr. Shin-Han Shiu (Michigan State University Plant Genome Research Program) presented an overview of NSF's mission, funding priorities, and proposal review criteria. They emphasized the importance of aligning research with NSF's priorities, clearly articulating intellectual merit and broader impacts, and engaging with program directors early in the proposal development process. The officers also provided tips on proposal writing, including the use of one-pagers, addressing review criteria, and budgeting for broader impacts activities. They encouraged attendees to sign up for NSF updates, participate in virtual office hours, and consider reviewing proposals to gain insights into the NSF peer review process.  Additional recommendations are to:

• Check current NSF priorities and executive orders for broader impacts activities
• Sign up for NSF news and updates for new funding opportunities
• Participate in NSF virtual office hours for division-specific topics
• Consider serving as NSF reviewers for proposal reviews

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

11:30 – 11:50 AM – Dr. Chi Chen, University of Minnesota, presented research on the differences in milk composition between contemporary and unselected dairy cows, focusing on fat content and its implications for nutrition. The study found that contemporary cows produce milk with higher levels of preformed fatty acids, while unselected cows produce milk with more medium-chain fatty acids. Chi also discussed the health implications of these differences, particularly regarding liver function and energy balance in early lactation. The research suggests that genetic selection for milk production has altered the fatty acid composition of milk, potentially impacting human health.

11:55 – 12:15 PM - Ahmed Darwish, Texas A&M University, presented his research on the omics-based discovery of horticultural biomarkers for human health. He discussed two main projects: one on muscadine grapes focusing on anti-angiogenic compounds for triple-negative breast cancer, and another on blueberries investigating their ability to modulate gut microbiome for cancer treatment. The muscadine grape research identified nine biomarker compounds with significant anti-cancer activity, while the blueberry project is in its early stages, exploring the effects of different developmental stages on phenolic content and potential gut microbiome modulation. Ahmed presented his research on compounds derived from seeds that show cytotoxic effects on cancer cells at 100 nanomolar concentration within 24 hours.

1:20 – 1:40 PM - Jian Yang, University of Guam, shared findings on the biological and phytochemical properties of plants used traditionally in Guam for health practices. Her research presented explored fractionation of plant extracts and computational methods to identify bioactive compounds. Next steps are to consider conducting anti-inflammatory assays on Guam plant extracts in future research to explore fractionation of plant extracts and computational methods to identify bioactive compounds.

1:45 – 2:05 PM - Mohit Verma, Purdue University, presented research on a smart capsule designed to sample and analyze the gut microbiome, particularly for applications in inflammatory bowel disease. The capsule can open at different pH levels to collect samples, and initial testing in pigs showed successful sampling in the large intestine.  Next steps are to consider future project to analyze differences between grass-fed and conventionally produced dairy products and to explore potential collaborations for biosensor applications in animal health.

2:10 – 2:30 PM – Patricia Wolf, Purdue University, discussed her research on sulfur metabolism and its link to colorectal cancer disparities, particularly focusing on how dietary choices and social determinants impact microbial sulfur metabolism and cancer risk. The two researchers explored potential collaborations, including Patricia's ongoing studies on cysteine metabolism and Mohit's work on biosensors for one health applications. The two researchers explored potential collaborations, including Patricia's ongoing studies on cysteine metabolism and Mohit's work on biosensors for one health applications.  Next steps are to conduct fecal microcosm experiments using labeled cysteine as part of the ACS Grant, to submit USDA Grant proposal to study sulfate in the diet and to optimize mass spectrometry methods for bile acid metabolite analysis.

2:35 – 2:55 PM - Brandon Pearson, Oregon State University, discussed his work on environmental contributions to neurological disorders, focusing on the use of African turquoise killifish as a model organism to study aging and neurodegenerative diseases. He also presented research on the presence of micro and nanoplastics in human cerebral spinal fluid and their potential link to dementia. Next steps are to share findings on nanoplastics in human cerebral spinal fluid and to continue studying how nanoplastics and adsorbed chemicals affect cellular toxicity.

3:40 – 4:00 PM - Ezgi Ozcan, Louisiana State University, presented her research on the effects of dietary compounds on gut microbiome and brain health, particularly regarding ketogenic diets and their impact on gut-brain axis communication. The discussion included details about their studies using mouse models to examine how different types of ketogenic diets affect microbiome composition in the small intestine and cecum, with particular attention to MCT-enriched diets. The group also discussed analytical methods for measuring bile acid metabolites and potential immunomodulatory effects, with Patricia offering to provide guidance on standards and testing approaches.

4:05 – 4:25 PM - Siva Kolluri, Oregon State University, presented work on a new compound targeting the Ah receptor for triple-negative breast cancer treatment, which showed promising anti-cancer effects in combination with flavonoids. The compound has unique metabolic properties and synergistic effects with other molecules.

4:30-5:00PM - Closing discussion on grant feedback, themes, collaborative proposal ideas or joint collaborative review articles based on topics/themes from the meeting

Discussion of research focused on the topic areas below:

• Horticultural Biomarkers for Human Health
• Cancer-Targeting Seed Compounds Research
• Milk Fatty Acid Composition Research
• Smart Capsule for Gut Microbiome
• Research on Health and Environment
• Ketogenic Diets and Gut Microbiome
• Ah Receptor Cancer Research Updates

Friday, September 12, 2025:

8:30-11:00 AM - Business Meeting, Corvallis, OR

• Assignment of W5122 group leadership roles for 2026
• Guidelines for assembly of the Annual Report
• Vote on location for next year’s meeting - Granlibakken Tahoe

Activities/Accomplishments:

Objective 1: Examine the effects of phytochemicals and other dietary components on gut microbiota and intestinal function.

W5122 researchers in Indiana (Verma) developed tools for probing the microbiome.  Despite several reports of gut microbiome composition and function, most studies have focused on fecal microbiome and limited knowledge is available about the microbiome in the other parts of the gastrointestinal (GI) tract. We have developed and tested a smart capsule that can collect samples from different parts of the GI tract (small and large intestine) while keeping the contents intact (especially the microbiome). In pig models, we demonstrated that the sample collected from the capsule matched the microbiome composition from sacrificed animal tissues at the expected locations. We also demonstrated that a similar approach can be used to detect levels of inflammation through changes in oxygen-reduction potential using a capsule. Thus, these tools have the potential to decipher the gastrointestinal microbiome in new ways. We demonstrate that a smart capsule can sample microbiome from inaccessible regions of the gastrointestinal tract. Thus, we have added a new potential tool for healthcare professionals and gut researchers to probe the microbiome.

W5122 researchers in California (Marco) investigated functional properties of microorganisms in fermented foods and digestive tract. This term we identified and measured compounds in fermented cabbage that support healthy gut barrier function. In another study, we found that one of the compounds enriched in fermented cabbage, indole-3-lactate (ILA), was similarly enriched in the intestine by probiotic lactobacilli and bifidobacteria. That study also elucidated how intestinal epithelial barrier repair is induced by ILA via specific cellular and immune pathways in the mammalian gut. We showed that such changes are ultimately affected by dietary intake, including the consumption of specific amino acids. These studies were complemented by our publication on teaching resources and extensive literature reviews on fermented dairy foods, lactobacilli, dominant microorganisms in fermented foods and probiotics, and examinations of clinical study literature which show how background diet is largely ignored studies on biotics such as fermented foods, probiotics and prebiotics.

W5122 researchers in Texas (Darwish) utilized omics-based discovery of horticultural biomarkers for human health. This term he made progress on two main projects: one on muscadine grapes focusing on anti-angiogenic compounds for triple-negative breast cancer, and another on blueberries investigating their ability to modulate gut microbiome for cancer treatment. The muscadine grape research identified nine biomarker compounds with significant anti-cancer activity, while the blueberry project is in its early stages, exploring the effects of different developmental stages on phenolic content and potential gut microbiome modulation. In addition, he found compounds derived from seeds show cytotoxic effects on cancer cells at 100 nanomolar concentration within 24 hours.

W5122 researchers in Connecticut (Chun) synthesized our data and existing scientific evidence to clearly define how beneficial compounds found in blackcurrants interact with the gut microbiome—the bacteria in the digestive system—to improve bone metabolism and reduce age-related bone loss. This crucial synthesis helped us successfully complete our project goals by validating the potential for dietary intervention, identifying the remaining key knowledge gaps, and creating a strong foundation for a large-scale clinical trial proposal to further advance this research.  Although blackcurrant consumption is associated with health benefits, the specific metabolic mechanisms and biomarkers responsible for its impact on conditions like bone and cardiovascular disease (CVD) remain poorly defined. This lack of understanding prevents personalized and effective dietary recommendations, which this project addresses by identifying host and microbial metabolic profiles that mediate the diet-health link. The findings from this project provided valuable, actionable information to a broad audience, including researchers, public health educators, and the food industry. We demonstrated that daily blackcurrant consumption over six months can positively modulate the gut microbiome and boost the production of beneficial microbial compounds, such as short-chain fatty acids. For the general public, especially adult women interested in preventing bone aging, this research offers a clear, non-pharmaceutical dietary strategy to help mitigate the risk of postmenopausal bone loss. Furthermore, a significant benefit of this grant was the development of research capacity. We provided extensive training and professional development to several graduate and undergraduate students. They gained crucial expertise in advanced biomedical technologies, including gut microbiome sequencing, clinical trial design, and sophisticated bone mineral density measurement (DEXA), ensuring a highly skilled workforce is prepared to advance diet-health science.

W5122 researchers in Oregon (Maier) investigated gut enterotype-dependent modulation of gut microbiota and their metabolism in response to xanthohumol supplementation in healthy adults. We and others have shown in previous studies that Xanthohumol (XN), a polyphenol found in the hop plant (Humulus lupulus), has antioxidant, anti-inflammatory, prebiotic, and anti-hyperlipidemic activity. Our own and other work provided preclinical evidence that suggested the gut microbiome is essential in mediating these bioactivities; however, gaps on knowledge still exist on how XN mediates its biological effect and the role that the gut microbiome may play.  Our 2025 efforts focused on extending and contextualizing our recently completed human and mechanistic studies examining xanthohumol–microbiome interactions. Building on prior evidence of enterotype-dependent responses and microbiota-derived metabolites, ongoing analyses emphasize host–microbiome metabolic crosstalk and implications for gut and systemic health. As part of this ongoing collaboration, we extended our work on xanthohumol to define its interactions with gut microbiota under controlled eubiotic and dysbiotic conditions. Using gastrointestinal simulation models combined with targeted and untargeted mass-spectrometry-based metabolomics, this study demonstrated that xanthohumol alters microbial metabolic function, including short-chain fatty acid production and bile acid dynamics, through inhibition of microbial bile salt hydrolase activity (Jamison et al. 2025).

W5122 researchers in Nebraska (Izard) tested how milk fat globule membrane (MFGM) affects infant gut microbiota and immune markers. In a double-blind randomized trial, infants (7–18 days old) received standard bovine formula (Control), the same formula with bovine MFGM (5 g/L; INV-MFGM), or mother’s own milk (HM) for 60 days. Oral and stool samples (baseline and Day 60) were analyzed for microbiota, immune markers, and metabolites. At Day 60, formula-fed infants had higher stool diversity/richness than HM and higher abundance of Bifidobacterium bifidum and B. catenulatum. Stool pH was higher in Control vs HM, while INV-MFGM showed higher acetate, propionate, isovalerate, and total short- and branched-chain fatty acids vs HM; butyrate and lactate increased over time in INV-MFGM. No differences were found in oral microbiota or measured immune markers, though sIgA rose over time in all groups. Overall, MFGM modestly shifted stool microbiota and fatty acid profiles, and early nutrition produced distinct gut development patterns.

W5122 researchers in Louisiana (Ozcan) investigated the effects of dietary medium chain triglycerides (MCT) on gut microbiota. We first determined region-specific impacts of MCTs in ketogenic diet along the gastrointestinal tract and discovered that MCT caused more pronounced shifts in the small intestine than in cecum. To further explore specific microbial responses, we employed in vitro microbial growth tests. We showed that MCT, palm, and coconut oils at concentrations above 5% v/v suppressed Lactiplantibacillus plantarum growth. These early findings will guide future research on oil–microbe interactions and brain health.

Objective 2: Identify cellular mechanisms and molecular targets of beneficial or adverse dietary components that influence human health.

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 researchers in Oregon (Tilton) evaluated the role of combined environmental factors associated with inflammation from pre-existing disease and polycyclic aromatic hydrocarbon (PAH) exposure on pulmonary toxicity. Primary human bronchial epithelial cells were utilized as a physiologically relevant model to evaluate the effects of inflammation on toxicity of benzo[a]pyrene (BaP). 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. 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.  In this case, the effects of BaP were observed in an asthmatic lung model compared to healthy lung cells and a strong interaction was observed for the effect of BaP on asthmatic cells related to barrier integrity, mucus production, goblet cell hyperplasia, type 2 asthmatic inflammation and chemical metabolism. Additional studies are exploring the role of non-coding miRNAs as mediating BaP toxicity in cells.  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) completed studies to improve our understanding of the pharmacokinetics of PAH exposure in a physiologically relevant 3D in vitro human orgnanotypic culture model. A quantitative understanding of chemical dosimetry is key for interpreting and extrapolating study results; however, dosimetry is understudied in organotypic models limiting ability to predict toxicity. We developed a dosimetry model using BAP. Dose and time course evaluation of metabolite formation and enzyme activity and expression were utilized to parameterize a cellular dosimetry model to improve the utility of 3D models for assessing chemical risk. Dosimetry analysis demonstrated absorption of BAP into cells and an increase in Phase 1 and 2 metabolites over time that correlated with regulation of metabolizing enzymes. This study demonstrates the usefulness of complex in vitro systems for human-relevant toxicity data and exhibits how in silico models can be utilized for understanding the dosimetry of test compounds to aid in in vitro to human extrapolation of toxicity data for risk assessments.

W5122 researchers in Oregon (Pearson) investigated how pesticides and nanoplastics affect neurological disease risk in animal and cellular models. Ongoing collaborations with researchers in Germany are evaluating how generational dietary factors contribute to aging phenotypes and health in offspring generations.

W5122 researchers in Oregon (Maier) evaluated how Caffeoylquinic acids and triterpenoids, both present in C. asiatica aqueous extracts, are bioactive constituents contributing to antioxidant protective mechanisms and neurotrophic activity. C. asiatica has been associated with improving mental health and cognitive function. During the reporting period, our group continued collaborative research on the chemical characterization, standardization, and stability of Centella asiatica aqueous extracts (CAW), in close collaboration with BENFRA investigators at OHSU and other academic institutions. Specifically, we contributed targeted mass-spectrometry-based methods to define CAW bioactive composition and ensure rigor and reproducibility in behavioral and mechanistic studies. We developed and applied LC–MRM–MS workflows to quantify major triterpenes (TTs) and caffeoylquinic acids (CQAs) in CAW materials used across animal studies. Our long-term goals relate to developing methods for botanical authentication, compositional characterization, thereby enabling linking chemistry to biological activity and enhancing the rigor of botanical efficacy studies by ensuring that highly characterized botanical extracts are used. As part of those efforts, we played a central role in evaluating the stability of CAW-derived compounds under experimental handling conditions, providing essential data for study design and interpretation (Hack et al, 2025).

W5122 researchers in Oregon (Maier) established omics-driven cultivation and standardization strategies for Centella asiatica, supporting reliable production of botanicals with defined chemical and biological profiles relevant to human health. In parallel, we continued collaborative research on Centella asiatica focused on botanical quality, reproducibility, and chemical drivers of bioactivity. Through metabolomics-based profiling of greenhouse-grown Centella cultivars, we demonstrated that genetic background, cultivation conditions, and harvest timing strongly influence the production of key triterpenoids and phenolic metabolites. This work provides a data-driven framework for cultivar selection and standardization of botanical materials, supporting W5122 objectives related to chemical characterization, safety, and consistency of food-derived bioactive compounds (Alam et al. 2025). Taken together, our research provides support that caffeoylquinic acids and triterpenoids, both present in C. asiatica aqueous extracts, are bioactive constituents that are associated with in vitro and in vivo observed antioxidant protective mechanisms and neurotrophic activity. Our contributions strive to integrate analytical chemistry and metabolomics for the characterization of plant materials to ensure reliable mechanistic studies of botanicals for preclinical and clinical work.

W5122 researchers in Oregon (Maier) performed chemical and mechanistic studies of Withania somnifera extracts finding that besides withanolides other non-withanolide compounds contribute to observed bioactivity and behavioral changes in preclinical models. We have continued investigating mechanisms of actions and potential targets of phytoconstituents in Withania somnifera (“ashwagandha”). Initial preclinical studies using Drosophila melanogaster as an in vivo whole-organism model support the hypothesis that non-withanolide constituents contribute to amelioration of age-related and stress-induced behavioral phenotypes. Ongoing collaborative work has expanded these efforts to include bioassay-guided fractionation of aqueous root and leaf extracts, followed by chemical characterization of fractions and testing in complementary biological systems, including cultured neuronal cell models and Drosophila behavioral assays. Analytical work is ongoing to delineate the phytochemical constituents present in these fractions using LC-HRMS/MS and targeted LC-MRM-MS approaches, with the goal of associating defined chemical signatures with bioactivity measures observed in age-related cognitive and functional preclinical models. Emerging evidence from these collaborative studies suggests that alkaloid-enriched fractions may play a previously underappreciated role in mediating neuroactive and stress-resilience effects of Withania somnifera.

W5122 researchers in Oregon (Tanguay) used zebrafish with carefully defined diets to dissect how specific nutrients, bioactives, and dietary toxicants alter cellular pathways, gene expression, and organ development that are conserved with humans. By integrating nutritional control with transcriptomic, behavioral, microbiome, and physiological readouts, the program identifies molecular targets and mechanisms—such as metabolic, stress-response, and gut–brain pathways—through which dietary components exert beneficial or adverse effects on health.

Objective 3: Explore the interaction between dietary components and the host metabolome and epigenome.

W5122 researchers in Minnesota (Chen) measured metabolite biomarkers linking diet quality, microbial metabolism, and diabetes risk. Unhealthy diet and microbiota dysbiosis are known risk factors of diabetes, but the value of microbial metabolites as indicators of diet quality and diabetes risk has rarely been explored. In this prospective study, we examined the associations of dietary intake and plasma metabolites with diabetes parameters in adults enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) study. A total of 2296 non-diabetic CARDIA participants were examined for diet quality, plasma metabolome components, fasting glucose, and insulin at year 7, and the occurrence of incident diabetes between years 7 and 25 of the study. Dietary intake was assessed by an interviewer-administered diet history. Diet quality was characterized by the healthy eating index 2020 (HEI2020) score. Spearman correlation analysis assessed the associations of plasma metabolites with HEI2020, fasting glucose, insulin, and homeostatic model assessment (HOMA) indexes. Subsequent propensity matching 131 incident diabetes cases with controls yielded a paired dataset for logistic and multivariate regression analyses. The predictive markers from these analyses were validated by Cox proportional hazard models on three sets of randomly selected samples from 2296 participants.  Among 611 plasma metabolites, cinnamoylglycine, produced jointly by microbial phenylalanine fermentation and hepatic glycine conjugation, was positively correlated with diet quality and inversely associated with incident diabetes risk. Isoleucine was inversely correlated with diet quality and positively associated with diabetes risk. This contrast between cinnamoylglycine and isoleucine provided a cinnamoylglycine/isoleucine (C/I) ratio as a predictive indicator of diet quality and incident diabetes risk, which was validated from the three randomly selected samples. The C/I ratio may be an effective indicator linking diet quality, microbial metabolism, and diabetes risk.

W5122 researchers in Minnesota (Chen) examined the profiles of milk lipidome from genetic selection of dairy cows. Genetic selection and improved nutrition and management practices have transformed the Holstein cow. This study examined the impacts of 50 years of selection on milk composition during early lactation by comparing milk from contemporary Holsteins (CH) and a unique population of unselected Holsteins (UH) that produce less than half as much milk as their CH herdmates. Multiparous UH and CH cows (n = 12/genotype) were housed in the same facility, fed the same diets and subjected to the same management procedures. Milk samples were collected weekly through to week 9 of lactation. The proximate composition of milk was determined by infrared spectroscopy and its lipidome by liquid chromatography–mass spectrometry and structural analysis. Data were analyzed as repeated measures using mixed-model procedures with the week of lactation as the repeated effect. An energy balance nadir occurred at week 1 for UH and CH cows but was more severe (−4.5 vs. −14.8 Mcal net energy per day, respectively) for the CH cows. Lipidomic comparison of the 50 most abundant triacylglycerols (TAGs) revealed that CH milk had more TAGs with at least two preformed fatty acids and fewer TAGs with at least two de novo synthesized fatty acids than UH milk. Fatty acid analysis revealed that the increase in preformed fatty acids in CH cows was responsible for the different TAG profiles in UH and CH milk. Furthermore, CH milk contained less free carnitine, short-chain acylcarnitines and lactic acid but more butyric and 3-hydroxybutyric acid than UH milk in early lactation. These results demonstrate that differences in energy balance were primarily responsible for the differences in milk composition between the UH and CH genotypes in early lactation.

Objective 4: Determine how food processing influences chemical composition to affect human health.

W5122 researchers in Minnesota (Chen) completed a chemometric survey on whole stillages and distillers dried grains with solubles (DDGS) from biofuel production. Distiller’s dried grains with solubles (DDGS) is the major co-product in corn-based bioethanol plants. As a staple feed ingredient for livestock and poultry, the nutrient profile of DDGS is well documented. However, the profile of the organic metabolites generated during the fermentation and production process has not been extensively characterized. In the current study, whole stillage (WS) and DDGS samples were collected from ten biofuel plants in the eight Midwestern states in the United States and analyzed for nutrient composition, and chemometric analysis using liquid chromatography-mass spectrometry (LC-MS) and multivariate analysis was used to quantify various organic metabolites. The protein, lipid, fiber, and ash concentrations of WS and DDGS samples were within the expected ranges of values. The LC-MS analysis of supernatants of WS and DDGS samples showed that proline, alanine, asparagine, glutamic acid, and glycine were the most abundant free amino acids, which was likely due to their high abundance in corn protein. Lactic and acetic acids were the most abundant organic acids. Several aldehydes and polyamines with highly variable concentrations were also found in samples, which were consistent with their roles as intermediate and fermentation-derived metabolites. Interestingly, the principal components analysis-based multivariate modeling revealed clustering of metabolites in WS and DDGS samples based on two different types of ethanol and co-product production platforms that utilize different amounts of enzymes and heat during the fermentation process. This processing-based separation was mainly driven by the differences in multiple essential amino acids. This is the first systematic characterization of WS and DDGS metabolomes, and the data may serve as useful reference values for future optimization of bioethanol processing and coproduct utilization.

W5122 researchers in Minnesota (Chen) examined the mass balance of deoxynivalenol (DON) in growing pigs under sulfonation-based mitigation treatments. Deoxynivalenol (DON) is a highly reactive epoxy-sesquiterpenoid mycotoxin commonly present in cereal feed ingredients. Sulfonation can de-crease the lipophilicity of DON, leading to lower bioavailability, but the exact impact of sulfonation on the mass balance and disposition of DON in pigs was not well de-fined. Individually housed growing pigs (n=48, 25.7 ± 1.6 kg) were allotted to 4 dietary treatments formulated to include approximately 1 ppm or 2 ppm DON, with or without a sodium metabisulfite (SM)-based feed additive. After 14 days of feeding, pigs were placed in metabolism crates for 3-d adaptation and then 3-d fecal and urine collection. On d 20, pigs were euthanized for collecting digesta samples from the stomach, jejunum, ileum, and cecum. The concentrations of DON, de-epoxy-DON (DOM), and three DON sulfonates (DONS-1, DONS-2, and DONS-3) in digesta, fecal, and urinary samples were determined by the liquid chromatography-mass spectrometry analysis. Data were analyzed using a mixed model with fixed effects of DON, SM, and their interaction, and random effects of block (6 pigs/block), group (12 pigs/group), and replicate. Results: Feeding DON-contaminated diets does-dependently increase DON in digesta (stomach, jejunum, and ileum), feces, and urine. The SM additive resulted in extensive conversion of DON to DONS in feed—primarily DONS-2, decreased DON (P < 0.05) in the stomach, jejunum, ileum, and urine, and increased DONS (P < 0.05) in digesta at all locations and feces, reduced urinary DON (P < 0.05) and increased urinary DOM (P < 0.05). Interactions between DON and SM (P < 0.05) were observed due to increased DONS formation under the higher DON dose. In the digestive tract, DONS-3 was converted to DONS-2 as higher abundance of DONS-3 in foregut digesta was shifted to more DONS-2 in hindgut digesta and fecal samples. Overall, the SM additive effectively reduced the bioavailability of DON in pigs by converting DON to DONS in feed and increasing its excretion in the forms of DONS in feces and DOM in urine while unabsorbed DONS underwent interconversion in the hindgut.

W5122 researchers in Nevada (Frese) worked to advance a mechanistic understanding of how dietary N-glycans shape gut microbiome compositions and how these structures can be isolated from existing dietary ingredients via enzymatic food processing strategies. This work examined prebiotic carbohydrates in terms of their structure, origin, and enzymatic accessibility within the gut microbiome, as well as how novel foods produced via precision fermentation may influence these structures relative to their natural analogs. A comparative N-glycomic analysis of common dietary protein ingredients demonstrated that protein source (e.g., animal vs. plant) and production system (i.e., bovine vs. precision-fermented) strongly shape N-glycan composition in the resulting food. Importantly, our focused comparison of bovine versus precision-fermented whey proteins further shows that novel protein production technologies alter glycosylation patterns, despite near-identical protein backbones, resulting in divergent microbiome outcomes in vitro. Comparative testing of these N-glycoproteins across gut microbiome types worked to begin the articulation of a mechanistic framework linking glycan chemistry, gut microbial enzymes, and ecological outcomes. This included a bioinformatic method to enzyme prediction and enzyme production directly from gut microbiomes, as well as the characterization of novel endo-beta-N-acetylglucosaminidases from human gut microbiomes for their use in novel food processing approaches. Finally, this work was complemented by a comprehensive review of prebiotic substrates that synthesizes the field’s understanding of how selective microbial utilization is dictated by glycan fine structure, including monosaccharide composition, linkage type, branching, and polymer length, rather than carbohydrate class alone. This broadens the prebiotic concept to summarize our new information on freed N-glycans derived from dietary glycoproteins, positioning them as conditionally accessible substrates whose bioactivity depends on microbial enzymatic capacity and food processing status.

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.

Plans for 2025-2026:

W5122 researchers in Minnesota (Chen) plan to examine more metabolic events associated with the feedings of palm oils and bile acids in animals, and fecal transplantation in humans. In addition, we are expanding the chemometric analysis on oxidized oils and fats, DDGS, and fermented soybean meals.

W5122 researchers in Indiana (Verma) are developing additional tools for probing microbiomes in situ.

W5122 researchers in California (Marco) will focus on new studies to understand the quality aspects of fermented foods and the foods used to make them. We will also examine how specific microbial species in fermented foods and their relatives can support health by assessing them at the strain level. We are also continuing to work on the gut microbiome and probiotics to elucidate how microbial consortia and the compounds they produce can improve systemic health through the digestive tract.

W5122 researchers in Oregon (Tilton) will continue with studies to identify important mechanisms related to the adverse effects of dietary components on human health. 

W5122 researchers in Colorado (Chicco) will utilize the novel Fads2LoxP mouse model recently developed to investigate the impact of cardiac- and liver-specific Fads2 expression on myocardial ischemic tolerance (heart attacked size) in the context of high and low dietary omega-6 fatty acid intake.

W5122 researchers in Texas (Darwish) will continue to explore the effects of different developmental stages of blueberries on phenolic content and potential gut microbiome modulation.

W5122 researchers in Nevada (Frese) are working to more deeply characterize the metagenomic and meta-transcriptomic responses of gut microbiomes to N-glycoproteins using a new, local cohort of individually phenotyped metagenomes/metabolomes and in vitro experimentation. The team is also working to characterize additional enzymatic processing approaches that enhance, expand, and otherwise personalize N-glycan structures for prebiotic activity.

W5122 researchers in Oregon (Pearson) will incorporate gut microbiome research to understand its mediating role in exposure to health outcome relationships.

W5122 researchers in Connecticut (Chun) will perform additional analyses including microbial analyses to explore potential bacterial species related to the production of SCCAs and phytoestrogen metabolites as well as genetic testing as some SCCAs have been shown to reduce the expression of inflammatory genes. Additionally, they plan to perform multi-omics analysis to further elucidate the mechanism of action of BC on prevention of postmenopausal bone loss in the study population.

W5122 researchers in Oregon (Maier) will complete the data analysis of the experimental work and publish new methodology and results on which compound classes found in those compositionally complex extracts exert certain bioactivity. We will continue investigating compounds present in hops for their health promoting properties and mode of actions and targets in the context of Inflammatory Bowel Disease and gut microbiota host interactions.

W5122 researchers in Oregon (Tanguay) will expand its high-throughput zebrafish platforms to perform more predictive toxicology, systematically testing how specific nutrients, bioactives, and dietary toxicants influence conserved cellular, metabolic, and neurobehavioral pathways, with and without microbiome involvement. By integrating deep-learning behavioral analytics, multi-omics readouts, and big-data modeling, these studies will identify molecular targets and signatures that both explain mechanism and improve prediction of beneficial or adverse dietary effects on human health.

W5122 researchers in Nebraska (Izard) will investigate the importance of the colonoic space in the diet-microbiome-energy axis.

W5122 researchers in Hawaii (Nerurkar) plan to refine techniques to biofortify active compounds and minerals in tropical vegetables used as functional foods and identify alternate approaches to grow these vegetables in Controlled environment using technology to optimize plant growth, quality, and production efficiency

W5122 members and their labs were supported by 43 grants from federal agencies, private foundation, industry collaborations, and institutional investments totaling over $24.7M during the 2024-25 period to study effects of bioactive nutrients on cancer, diabetes, fetal programming by maternal diet, gut health, and cardiovascular risk). Major awards from this reporting period are listed below.

There were 90 new publications by W5122 members in 2024-2025 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.

1. Zhang J, Yao D, Shurson GC, Chen C. Chemometric Characterization of Whole Stillage and Distillers Dried Grains with Solubles from Industrial Bioethanol Production Reveals the Impacts of Processing on Fermentation Metabolites. J Agric Food Chem. 73, 28262 (2025) DOI: 1021/acs.jafc.5c08081
2. Yin R, Sargsyan D, Wu R, Hudlikar R, Li S, Kuo HC, Sarwar MS, Zhou Y, Gao Z, Howell A, Chen C, Blaser MJ, Kong AN. Microbiome and Metabolome Alterations in Nrf2 Knockout Mice with Induced Gut Inflammation and Fed with Phenethyl Isothiocyanate and Cranberry Enriched Diets. Molecular Nutrition & Food Research e70283 (2025) https://doi.org/10.1002/mnfr.70283
3. Steffen BT, Lusczek ER, Jacobs Jr DR, Chen C, Murthy VL, Van Horn L, Terry JG, Carr JJ, Steffen LM. No Evidence of Metabolomic Disruptions From Real-World Intakes of Aspartame or Saccharin: The Coronary Artery Risk Development in Young Adults Study. J Diabetes 8, e70138 (2025) https://doi.org/10.1111/1753-0407.70138
4. Ding F, Weber WJ, Su R, Crooker BA, Chen C. Effect of Holstein Genotype and Energy Balance on Lipids, Carnitine and Short-Chain Carboxylic Acids in Milk During Early Lactation. Lipidology 2, 6 (2025) https://doi.org/10.3390/lipidology2010006
5. Mosher W, Yao D, McGhee M, Giesting DW, Faris RJ, Chen C. Differential Dispositions of Deoxynivalenol in Nursery and Finishing Pigs under Sulfonation Treatment Revealed by Metabolomic Profiling. ACS Agricultural Science & Technology. 2025 https://doi.org/10.1021/acsagscitech.4c00677
6. Kerr BJ, Wilson VC, Zhang J, Chen C. Influence of feeding thermally peroxidized lipids on the performance of growing pigs. J Anim Sci, 103, skaf015 (2025) DOI: 1093/jas/skaf015
7. Boardman K, Sun X, Yao D, Chen C, van Lierop L, Hu B. Increasing the Nutritional Value of Camelina Meal via Trametes versicolor Solid-State Fermentation with Various Co-Substrates. Fermentation 11, 77 (2025) https://doi.org/10.3390/fermentation11020077
8. Guse K, Mao Q, Chen C, Gomez A. Meta-Omics Analyses of Conventional and Regenerative Fermented Vegetables: Is There an Impact on Health-Boosting Potential? Fermentation11, 22 (2025) https://doi.org/10.3390/fermentation11010022
9. Johnson AJ, Li W, Dittrich BI, Cole AC, Prodell MK, Lyons JW, Fritz SA, Fregulia P, Chen C, Kwon CH, Jang YD. Effect of second iron injection on growth performance, hematological parameters, and fecal microbiome of piglets fed different dietary iron levels. J Anim Sci, 103, skae371 (2025) https://doi.org/10.1093/jas/skae371
10. Whitcomb LA, Berry K, LaVergne SM, Natter N, Baxter BA, Rao S, Tipton M, Gritsenko MA, Weitz KK, Gerbasi V, Bramer L, Piehowski P, Webb TL, Henao-Tamayo M, Chicco AJ, Dunn J, Dutt TS, Ryan EP.  Blood pro-thrombotic analytes and platelet activation are associated with post-acute sequelae of COVID-19. BMC Infectous Dis, In press1186/s12879-025-11824-3
11. Dolan CC, Whitcomb LA, Del Carpio E, Rose L, Chicco AJ, Crans DC. How vanadium and manganese compounds impact cardiac mitochondrial function. Front Chem Biol DOI 10.3389/fchbi.2025.1602602
12. * Fresa KJ, Catandi GD, Gonzalez-Castro RA, Omar A, Whitcomb LA, Cheng M-H, Chen TW, Carnevale EM,Chicco AJ. Impact of dietary essential fatty acids on phospholipid composition and mitochondrial function in aged mares.  Sci Rep  15:43295, 2025.
13. Asma K Omar AK, Li Puma LC, Risk BD, Witt AC, Izon CS, Whitcomb LA, Kareng DJ, Winger QA, Bouma GJ, Chicco AJ. Validation of an ovine model for studying impacts of prenatal docosahexaenoic acid supplementation on fetal tissue membrane composition and metabolism. J Nutri Biochem Oct 4:110137. doi: 10.1016/j.jnutbio.2025.110137. PMID: 41052657
14. Mueller RL, Li Puma LC, Itgen MW, Chicco AJ. Evolutionary diversity of muscle OXPHOS efficiency across ectothermic vertebrates. R. Soc. B 292:20250374, 2025. /doi.org/10.1098/rspb.2025.0374
15. Nunes LGA, Weingrill RB, Fredrick SBJ, Lorca R, Lee M-J, Atif SM, Chicco AJ, Rosario FJ, Urschitz J. Trophoblast‐specific Deptor knockdown enhances trophoblast nutrient transport and fetal growth in mice. Acta Physiologica. 241:e70012, 2025. https://doi.org/10.1111/apha.70012
16. Zhu C, Whitcomb LA, Chicco AJ, Gravely ME, Alcocer HM, Alambarrio DA, Gonzalez JM,  Smith CL, Nair MN, Loh HY, Engle TE, Niraula A, Zhai C. Nicotinamide Riboside Supplementation Affects Postmortem Mitochondrial Functionality and Apoptotic Activation Metabolites15:31,2025; PMID: 39852374
17. Tait C, Chicco AJ, Naug D. Brain energy metabolism as an underlying basis of slow and fast cognitive phenotypes in honeybees J Exp Biol227 (17):247835, 2024. PMID: 39092671
18. Fresa KJ, Catandi GD, Whitcomb LA, Gonzalez-Castro RA, Chicco AJ, Carnevale EM. Adiposity in mares induces insulin dysregulation and mitochondrial dysfunction which can be mitigated by nutritional intervention.  Sci Rep14:13992, 2024. PMID: 38886475
19. Catandi GD, Fresa KJ, Cheng MH, Whitcomb LA, Broekling CD, Chen TW, Chicco AJ, Carnevale EM.  Follicular metabolic alterations are associated with obesity in mares and can be mitigated by dietary supplementation. Sci Rep 14:7571. 2024. PMID: 38555310
20. Gonzalez K, Merlin AC, Roye E, Osidele A, Ju B, Lee Y, Chicco AJ,Chung E. Voluntary Wheel Running Reduces Cardiometabolic Risks in Female Offspring Exposed to Lifelong High-Fat, High-Sucrose Diet. Med Sci Sport Exerc; 2024. PMID: 38595204
21. Kim, T., Palla, G., Raut, B., Verma, M.S., Ardekani, A. (Submitted: 24 September 2025) Evaluation of Paper-based Loop-Mediated Isothermal Amplification Submitted to Analytical Chemistry.
22. Kamel, M.K., Davidson, J.L., Dextre, A., Ault, A., Pillai, D., Koziol, J., Schoonmaker, J.P., Johnson, T.A., Verma, M.S.* (Submitted: 23 October 2025) Development and evaluation of novel quantitative PCR (qPCR) and loop-mediated isothermal amplification (LAMP) assays for bovine adenovirus type 7 Submitted to The Veterinary Journal.
23. Davidson, J.L., Maruthamuthu, M.K., Kamel, M., Mohan, S., Pascual-Garrigos, A., Dextre, A., Centeno-Delphia, R.E., Boerman, J.P., Pillai, D., Koziol, J., Ault, A., Schoonmaker, J.P., Johnson, T.A., Verma, M.S.* (Submitted: 29 July 2025) Detection of five viruses commonly implicated with Bovine Respiratory Disease using loop-mediated isothermal amplification Submitted to Veterinary Quarterly.
24. Athalye, S.M., Maruthamuthu, M.K., Esmaili, E., Boodaghidizaji, M., Raffaele, J., Selvamani, V., Smith, J.P., Matos, T., Rustandi, R., Ardekani, A., Verma, M.S.* (2026) Real-time monitoring of attenuated cytomegalovirus using Raman spectroscopy allows non-destructive characterization during flow Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 345, 126761, DOI: 10.1016/j.saa.2025.126761
25. Rafiq, N., Verma, M.S.* (2025) Design and development of a field-deployable water bath for loop-mediated isothermal amplification assay IEEE Sensors Journal. DOI: 10.1109/JSEN.2025.3588790
26. Ahmed, B., Raut, B., Pauley, A., Davidson, J.L., Yang, S., Verma, M.S.* (2025) Development of a Portable Paper-based Biosensor for the Identification of Genetically Modified Corn (Zea mays) and Soybean (Glycine max) Biosensors and Bioelectronics 287, 117690. DOI: 10.1016/j.bios.2025.117690
27. Kamel, M., Davidson, J.L., Schober, J.M., Fraley, G.S., Verma, M.S.* (2025) A paper-based loop-mediated isothermal amplification assay for highly pathogenic avian influenza Scientific Reports 15, 12110. DOI: 10.1038/s41598-025-95452-6
28. Mayorga, C., Athalye, S.M., Boodaghidizaji, M., Sarathy, N., Hosseini, M., Ardekani, A., Verma, M.S.* (2025) Limit of detection of Raman spectroscopy using polystyrene particles from 25 to 1000 nm in aqueous suspensions ACS Analytical Chemistry 97, 16, 8908–8914. DOI: 10.1021/acs.analchem.5c00182
29. Kaur, S., Bran, L., Rudakov, G., Wang, J., Verma, M.S.* (2025) Propidium monoazide is unreliable for quantitative live-dead molecular assays ACS Analytical Chemistry 97, 5, 2914-2921. DOI: 10.1021/acs.analchem.4c05593
30. Wickware, C., Ellis, A.C., Verma, M.S., Johnson, T.A.* (2025) Phenotypic antibiotic resistance prediction using antibiotic resistance genes and machine learning models in Mannheimia haemolytica Veterinary Microbiology 302: 110372 DOI: 10.1016/j.vetmic.2025.110372
31. Ranjbaran, M., Kaur, S., Wang, J., Raut, B., Verma, M.S.* (2024) A drop dispenser for simplifying on-farm detection of foodborne pathogens. PLoS One 19(12): e0315444. DOI: 10.1371/journal.pone.0315444
32. Kevin Whelan, Margaret Alexander, Claire Gaiani, Genelle Lunken, Andrew Holmes, Heidi M Staudacher, Stephan Theis, Maria L Marco. 2024. Design and reporting of prebiotic and probiotic clinical trials in the context of diet and the gut microbiome. Nature Microbiology. 9(11):2785-2794. https://doi.org/10.1038/s41564-024-01831-6
33. Aviaja Hauptmann, Stephany Maroney, Jessica Bissett Perea, Maria L Marco. 2025. Growing microbiology literacy through interdisciplinary and Indigenous human rights frameworks. Journal Microbiology and Biology Education. 26(1):e0015224 https://doi.org/10.1128/jmbe.00152-24
34. Lei Wei, Wannes Van Beeck, Melanie Hanlon, Erin DiCaprio, Maria L Marco. 2025. Lacto-fermented fruits and vegetables: bioactive components and effects on human health. Annual Review of Food Science and Technology. 16(1):289-314 1146/annurev-food-052924-070656
35. Clarissa Santos Rocha, Katie L Alexander, Carolina Herrera, Mariana G Weber, Irina Grishina, Lauren A Hirao, Dylan J Kramer, Juan Arredondo, Abigail Mende, Katti R Crakes, Anne N Fenton, Maria L Marco, David A Mills, John C Kappes, Lesley E Smythies, Paul Ziprin, Sumathi Sankaran-Walters, Phillip D Smith, and Satya Dandekar. 2025. Microbial remodeling of gut tryptophan metabolism and indole-3-lactate production regulate epithelial barrier repair and viral suppression in human and simian immunodeficiency virus infections. Mucosal Immunology. S1933-0219(25)00011-X. doi: 10.1016/j.mucimm.2025.01.011
36. Lei Wei and Maria L Marco. 2025. The fermented cabbage metabolome and its protection against cytokine-induced intestinal barrier disruption of Caco-2 monolayers. Applied Environmental Microbiology 91(5):e0223424. https://doi.org/10.1128/aem.02234-24
37. Alejandra Mejía-Caballero and Maria L Marco. 2025. Lactobacilli biology, applications and host interactions. Nature Reviews Microbiology. https://doi.org/10.1038/s41579-025-01205-7
38. Glory Bui and Maria L Marco. 2025. Impact of fermented dairy on gastrointestinal health and associated biomarkers. Nutrition Reviews. Jul 24:nuaf114. doi: 10.1093/nutrit/nuaf114
39. Supatirada Wongchanla, Kunal Dixit, Sangwoo Park, Kwangwook Kim, Shuhan Sun, Maria L Marco, Steven B. Palomares, Alejandra Mejia‑Caballero, Sahana Mohan, Xunde Li, Xiaojing Li,  and Yanhong Liu. 2025. Effects of dietary L‑glutamate and L‑aspartate supplementation on growth performance, severity of diarrhea, intestinal barrier integrity, and fecal microbiota of weaned piglets challenged with F18 enterotoxigenic Escherichia coli. Journal of Animal Science and Biotechnology. 16:131 https://doi.org/10.1186/s40104-025-01266-x
40. Valdez R, Chang Y, Pennington JM, Tilton SC. 2025. MicroRNA mediated changes in susceptibility for benzo[a]pyrene toxicity in a 3D respiratory model for asthma. Accepted to Current Res. Toxicol.
41. Burns K, Biggerstaff A, Pennington JM, Anderson KA, Tilton SC. 2025. Co-culture of primary human bronchial epithelial cells at the air-liquid interface and THP-1 macrophages to investigate the toxicity of polycyclic aromatic hydrocarbons. Toxics, Special Issue “Emerging Pollutants in the Air and Health Risks”.  13(12), 1065; doi.org/10.3390/toxics13121065. PMCID: PMC12737494.
42. Colvin V, Bastin K, Siddens LK, Maier ML, Williams DE, Smith JN, Tilton SC. 2025. Building a Predictive Model for PAH Dosimetry in ALI-HBECs using Benzo[a]pyrene. Reports. 15:102133. doi.org/10.1016/j.toxrep.2025.102133. PMCID: PMC12517105.
43. Colvin V, Owiti NA, Engelward BP, Tilton SC. Utilization of the CometChip Utilization of the CometChip Assay for Detecting PAH-induced DNA Bulky Adducts in a 3D Primary Human Bronchial Epithelial Cell Model.  Toxicology. 517:154241. doi: 10.1016/j.tox.2025.154241. PMCID: PMC12356187.
44. 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:
45. 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. J. Mol. Sci. 25(8), 4326. doi.org/10.3390/ijms25084326. PMCID: PMC11050152.
46. Samy MN, Attia EZ, Khalifa BA, Darwish AG, Al-Karmalawy AA, Alnajjar R, Abdelmohsen UR, Ibrahim MA, Ross SA. Undescribed cytotoxic butenolides; asperterreunolides A-E, isolated from endophytic fungus Aspergillus terreus derived from Artemisia arborescens, supported with in silico study. Phytochemistry (2025).
47. Darwish AG, Das PR, Olaoye E, Gajjar P, Ismail A, Mohamed AG, Tsolova V, Hassan NA, El Kayal W, Walters KJ, El-Sharkawy I. Untargeted flower volatilome profiling highlights differential pollinator attraction strategies in muscadine. Front Plant Sci (2025).
48. Ismail A, Gajjar P, Darwish AG, Abuslima E, Islam T, Mohamed AG, Tsolova V, Nick P, El Kayal W, El-Sharkawy I. Redox and osmotic homeostasis: Central drivers of drought resilience in grapevine rootstocks. Plant Physiol Biochem (2025).
49. Ibrahem ES, Fahim JR, Samy MN, Darwish AG, Desoukey SY, Kamel MS, Ross SA. Chemical and Biological Investigation of Ceiba chodatii Flowers. Chemistry (2025).
50. Samy MN, Kemelbek M, Alshymaa AG, Darwish AG, Gauhar S, Samir AR. Isolation and chemical characterization of secondary metabolites from Gazania rigens and their antimicrobial and cytotoxic activities. Natural Product Research (2024).
51. O'Brien, C.E., Frese, S. (co-first)., Cernioglo, K., DamiaN-Medina, K., Mitchell, R.D., Casaburi, G., Melnyk, R.A., Henrick, B.M., Smilowitz, J.T. (2025). “Randomized, Placebo-Controlled Trial Reveals the Impact of Dose and Timing of Bifidobacterium infantis Probiotic Supplementation on Breastfed Infants’ Gut Microbiome.” https://doi.org/10.1128/msphere.00518-25
52. Yalçıntaş, Y.M., and Matthew J. Bolino, Duman, H, Sarıtaş, S., Pekdemir, B., Kalkan, A.E., Canbolat, A.A., Bolat, E., Eker, F., Rocha, J.M., Frese S.A.* & Sercan Karav (2025): Prebiotics: types, selectivity and utilization by gut microbes, International Journal of Food Sciences and Nutrition, https://doi.org/10.1080/09637486.2025.2582557.
53. Bolino, M., Duman, H., Avcı, İ., Kayili, H.M., Petereit, J., Salih, B., Karav, S. and Frese, S.* (2025) ‘Proteomic and N-glycomic comparison of synthetic and bovine whey proteins’, Microbiology Spectrum. https://doi.org/10.1128/spectrum.00200-25
54. Tatarko, A.R., Vannette, R., Frese, S. and Leonard, A.S. (2025). ‘A wild bumble bee shows intraspecific differences in sensitivity to multiple pesticides’, Royal Society Open Science. https://doi.org/10.1098/rsos.250281
55. Bolino, M., Haththotuwe Gamage, N., Duman, H., Abiodun, O., De Mello, A.S., Karav, S. and Frese, S.* (2025) ‘Novel Endo-β-N-Acetylglucosaminidases Derived from Human Fecal Samples Selectively Release N-Glycans from Model Glycoproteins’, Foods, 14(8), p.1288. https://doi.org/10.3390/foods14081288
56. Bolino, M., Avci, I., Kayili, H.M., Duman, H., Salih, B., Karav, S. and Frese, S.* (2025) ‘Identification and comparison of N-glycome profiles from common dietary protein ingredients’, Food Chemistry: X. https://doi.org/10.1016/j.fochx.2024.102025
57. Alipour, Z., Duman, H., Lee, J., Karav, S., & Frese, S. (2025). The microbiome in infant gut health and development. In Nutrition in the Control of Inflammation (pp. 29-49). Academic Press. https://doi.org/10.1016/B978-0-443-18979-1.00003-4
58. Lucey CM, Pearson BL, DeSantis K, GoldsmithJ, Halliday AN, Navas-Acien A, Schilling K, Basu  Isotopic fractionation of natural uranium in mice as a potential biomarker of renal accumulation (2025). Environmental Science & Technology 59, 28: 14279–14289.
59. Andrade-Feraud CM, Acanda de la Rocha AM, Berlow NE, Duque S, Holcomb B, Coats ER, Ghurani YR, Lucey CM, Pearson BL, Guilarte TR, Azzam DJ. (2025) Chronic arsenic exposure of ovarian surface and fallopian tube cultures induces giant and/or multinucleated cells with phagocytosis-like properties and an inflammatory phenotype. Toxicology and Applied Pharmacology500: 117394.
60. Xie K, Scifo E, Pearson B, Ryan D, Henzel K, Markert A, Schaaf K, Wang C, Mi X, Tian X, Bonn S, Schölling M, Möhl CO, Bano D, Zhou Y, Ehninger D. (2025). Intermittent fasting boosts sexual behavior by limiting the central availability of tryptophan and serotonin. Cell Metabolism37(5): 1189-1205.e7
61. Briana M. Nosal, Alexander Aksenov, Catherine Andersen, Elaine Choung-Hee Lee, Yanjiao Zhou, Ock K. Chun. The gut-bone axis: Potential influence of anthocyanins and implications for postmenopausal osteoporosis. Food Science and Biotechnology. (In press; Accepted on May 5, 2025). https://doi.org/10.1007/s10068-025-01907-x
62. Manije Darooghegi Mofrad, Seoeun Ahn, Ock K. Chun. The Interplay of Diet, Genome, Metabolome, and Gut Microbiome in Cardiovascular Disease and Mortality: A Narrative Review. Curr Med Chem 2025 Jan 6.  https://doi.org/10.2174/0109298673342364241119114722.
63. Alam MN, Marney L, Yang L, Choi J, Cerruti N, Techen N, Bassett S, Smith J, Brown K, Cabey K, Viswanathan R, Rajagopal S, Soumyanath A, Stevens JF, Maier CS. Clustering of chemical profiles of Centella asiatica cultivars, grown in greenhouses, allows grouping of metabolites with similar production trends. Ind Crops Prod. 2025 Sep 1;231:121159. doi: 10.1016/j.indcrop.2025.121159. Epub 2025 May 10. PMID: 40838195
64. Houriet J, Manwill PK, Magaña AA, Anderson VM, Beniddir MA, Bertrand S, Choi J, Clark TN, Foster LJ, Halabalaki M, Jarmusch AK, de Jonge NF, Khadilkar A, MacMillan JB, Maier CS, Marney LC, Marti G, Mikropoulou EV, Olivier-Jimenez D, Perez A, van der Hooft JJJ, Zdouc MM, Linington RG, Cech NB. Multilaboratory Untargeted Mass Spectrometry Metabolomics Collaboration to Identify Bottlenecks and Comprehensively Annotate A Single Dataset. Anal Chem. 2025 Aug 5;97(30):16110-16122. doi: 10.1021/acs.analchem.4c05577. Epub 2025 Jul 22. PMID: 40693864
65. Lin LW, Jang HS, Song Z, Ebrahimi A, Yang J, Nguyen BD, O'Donnell EF, Hendrix DA, Maier CS, Kolluri SK. Suppression of global protein synthesis and hepatocellular carcinoma cell growth by Benzimidazoisoquinoline, 4,11-Dichloro-BBQ. Biochem Pharmacol. 2025 Jun;236:116896. doi: 10.1016/j.bcp.2025.116896. Epub 2025 Mar 27. PMID: 40157458
66. Paraiso IL, Alcázar Magaña A, Alexiev A, Sharpton TJ, Maier CS, Kioussi C, Stevens JF. Reversing metabolic dysregulation in farnesoid X receptor knockout mice via gut microbiota modulation. PLoS One. 2025 Sep 5;20(9):e0331040. doi: 10.1371/journal.pone.0331040. eCollection 2025. PMID: 40911549 Free PMC article.     
67. Hack W, Kuhnau L, Martinez J, Marney LC, Choi J, Sohal AR, Koike S, Nguyen T, Maier CS, Soumyanath A, Gray NE. Triterpene and Caffeoylquinic Acid Constituents Contribute to the Cognitive-Enhancing, but Not Anxiolytic, Effects of a Water Extract of Centella asiatica in Aged Mice. Nutrients. 2025 Oct 8;17(19):3171. doi: 10.3390/nu17193171. PMID: 41097248 Free PMC article.     
68. Jamieson PE, Reichart NJ, Maier CS, Sharpton TJ, Bradley R, Metz TO, Stevens JF. Xanthohumol Alters Gut Microbiota Metabolism and Bile Acid Dynamics in Gastrointestinal Simulation Models of Eubiotic and Dysbiotic States. Int J Mol Sci. 2025 Nov 3;26(21):10698. doi: 10.3390/ijms262110698. PMID: 41226734
69. McDonald KL, Raichura Z, Pondugula SR, Marney L, Yang L, Choi J, Salamat JM, Brandes MS, Neff C, Adams K, Farmer G, Dennis C, Maier CS, Soumyanath A, Arnold RD, Calderón AI. Ashwagandha (Withania somnifera) Plant Extracts Affect the Cytochrome P450 System and Cytotoxicity of Primary Human Hepatocytes. J Diet Suppl. 2025;22(4):613-639. doi: 10.1080/19390211.2025.2514458. Epub 2025 Jun 24. PMID: 40551718; PMCID: PMC12266684.
70. Neiheisel S, Uchenik D, Marney L, Maier CS, Gray NE, Soumyanath A, Rakotondraibe HL. Development of a Proton Spin Network Fingerprint Library to Support Mass Spectrometry-Based Identification of Pharmacophore-Bearing Constituents in the Botanical Supplement Centella asiatica. J Nat Prod. 2025 Apr 25;88(4):975-984. doi: 10.1021/acs.jnatprod.4c01486. Epub 2025 Mar 28. PMID: 40152679; PMCID: PMC12060121.
71. Truong L, Bieberich AA, Fatig RO, 3rd, Rajwa B, Simonich MT, Tanguay RL. Accelerating antiviral drug discovery: early hazard detection with a dual zebrafish and cell culture screen of a 403 compound library. Arch Toxicol. 2025;99(3):1029-41. Epub 2024/12/28. doi: 10.1007/s00204-024-03948-3. PubMed PMID: 39730949; PMCID: PMC11821682.
72. Tanguay RL. The indispensable role of zebrafish as a new approach methodology (NAM) in toxicology. Toxicol Sci. 2025. Epub 2025/09/01 20:44. doi: 10.1093/toxsci/kfaf121. PubMed PMID: 40889284.
73. St Mary L, McClure R, Truong L, Carrell SJ, Waters KM, Tanguay RL. Phenotypically anchored transcriptomics across diverse agrichemicals reveals conserved pathways and unique gene expression signatures in zebrafish. Frontiers in Toxicology. 2025;7:1675060. Epub 2025/11/03. doi: 10.3389/ftox.2025.1675060. PubMed PMID: 41181350; PMCID: PMC12575134.
74. Rude CI, Smith JN, Scott RP, Schultz KJ, Anderson KA, Tanguay RL. A mixture parameterized biologically based dosimetry model to predict body burdens of polycyclic aromatic hydrocarbons in developmental zebrafish toxicity assays. Toxicol Sci. 2025;205(2):326-43. Epub 2025/03/21. doi: 10.1093/toxsci/kfaf039. PubMed PMID: 40117221; PMCID: PMC12118961.
75. Perone DM, Annalora AJ, Goldstone JV, Dickey AN, Salanga MC, Francolini RD, Wright FA, Marcus CB, Tanguay RL, Garcia-Jaramillo M. Zebrafish Cyp1b1 knockout alters eye and brain metabolomic profiles, affecting ocular and neurobehavioral function. Toxicol Appl Pharmacol. 2025;496:117246. Epub 2025/02/01 20:42. doi: 10.1016/j.taap.2025.117246. PubMed PMID: 39890032; PMCID: PMC12083501.
76. Morshead ML, Truong L, Tanguay RL. Position-Specific Methyl Substitution on Benzo[a]pyrene Drives AHR-Dependent Fin Duplication in Zebrafish. Toxicol Sci. 2025. Epub 2025/11/20. doi: 10.1093/toxsci/kfaf164. PubMed PMID: 41264521.
77. Morshead ML, Truong L, Simonich MT, Moran JE, Anderson KA, Tanguay RL. Developmental toxicity of alkylated PAHs and substituted phenanthrenes: Structural nuances drive diverse toxicity and AHR activation. Chemosphere. 2025;370:143894. Epub 2024/12/07. doi: 10.1016/j.chemosphere.2024.143894. PubMed PMID: 39643011; PMCID: PMC11732715.
78. Morshead ML, Truong L, Carrell SJ, Scott R, Anderson KA, Tanguay RL. Chemical structure drives developmental toxicity of alkyl-substituted naphthalenes in zebrafish. Environ Int. 2025;204:109837. Epub 2025/10/06. doi: 10.1016/j.envint.2025.109837. PubMed PMID: 41046622; PMCID: PMC12560828.
79. Morshead ML, Tanguay RL. Advancements in the Developmental Zebrafish Model for Predictive Human Toxicology. Curr Opin Toxicol. 2025;41. Epub 2025/02/03. doi: 10.1016/j.cotox.2024.100516. PubMed PMID: 39897714; PMCID: PMC11780918.
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