NIH research projects to track activities of gut-derived metabolites

Ten new research awards totaling nearly $4 million will allow researchers to study possible links between gut microflora and the transformation of dietary compounds into substances known as metabolites, which are made or used when the body breaks down food, drugs, or chemicals. This process creates energy and the materials needed for growth, reproduction, and maintaining health; it also helps to eliminate toxic substances. Small, gut-derived metabolites may ultimately serve as a way to explain the widely acknowledged health benefits of diets high in fruits and vegetables. The awards will be funded by the National Center for Complementary and Integrative Health (NCCIH), part of the National Institutes of Health.

“Evidence is building that the foods we eat, the gut microflora in our digestive systems, and our basic biological functions all intersect to influence our overall health,” said Craig Hopp, Ph.D., deputy director of the NCCIH Division of Extramural Research and lead scientific contact for these new grants. “These awards will allow us to systematically identify the metabolites in the diet‒microbiome interaction, the bacteria that produce them, and their related biological activities.”

Research conducted will fill current gaps in understanding regarding the abundance and variety of gut-derived metabolites and possible biological signatures associated with improved measures of health and resilience. These awards support model systems research and mechanistic clinical studies including:

• Fenugreek, Gut Microbiota, and Resiliency to Western Diet; Louisiana State University Pennington Biomedical Research Center, Baton Rouge; Dr. Annadora Bruce-Keller. This project will evaluate the effects of fenugreek seeds on intestinal microbiota and metabolite generation in order to identify novel mediators of resiliency versus vulnerability to Western-style diets. (Grant R01 AT010279)
• Mucosal Modulation by LGG and R. gnavus Specific Tryptophan Metabolites; Rutgers, The State University of New Jersey, Newark; Drs. Nan Gao and Ronaldo Paraoan Ferraris. This project will explore whether a specific probiotic (LGG) and the gut bacteria Ruminococcus gnavus metabolize dietary tryptophan and produce differential mucosal modulating effects via a hydrocarbon receptor signaling pathway. (Grant R01 AT010243)
• Flaxseed Effects on Gut Microbial Metabolism and Circulating Inflammation-related Metabolic Profiles in African American and Non-Hispanic White Women; Roswell Park Cancer Institute Corp., Buffalo, New York; Dr. Susan E. McCann. This project will characterize changes in microbial function and subsequent modification of circulating metabolic profiles related to chronic low-grade inflammation in a sample of African American and Non-Hispanic white women. (Grant R01 AT010216).
• Systems Biology of Microbe-mediated Glucosinolate Bioconversion in Inflammatory Bowel Disease; University of Virginia, Charlottesville; Dr. Jason Papin. This project will test if the conversion of plant glucoraphanin, an antioxidant, to bioactive sulforaphane, a chemical compound found in certain vegetables, by specific bacteria has mitigating effects on inflammatory bowel disease. (Grant R01 AT010253)
• Proanthocyanidin Metabolites Produced by Commensal Gut Microbes May Promote Metabolic Resilience; Rutgers, The State University of New Jersey; Dr. Diana E. Roopchand. This project will define the bioactivities of grape and berry polyphenol-derived microbial metabolites and identify the bacteria responsible for their production in both laboratory and clinical models. (Grant R01 AT010242)
• Dietary Flavonoids-Microbiota-Ah Receptor Interactions in the Gut; Texas A&M AgriLife Research, College Station; Drs. Stephen H. Safe, Robert Stephen Chapkin, Arul Jayaraman, and Kyongbum Lee. This project will identify flavonoid-derived microbial metabolites and explore their effects on a hydrocarbon receptor signaling pathway that helps maintain homeostasis in the lining of the gut. (Grant R01 AT010282)
• Multiomic Signatures of Microbial Metabolites Following Prebiotic Fiber Supplementation; Stanford University, Palo Alto, California; Dr. Michael P. Snyder. This project will expand the current understanding distinguishing the role of microbial- and host- generated metabolites in dynamic gut microbiota/host interaction of fecal transplants from human to germ-free and gnotobiotic animal models. (Grant R01 AT010232)
• Discovery and Biological Signatures of Microbiome-Derived Xanthohumol Metabolites and their Role in Ameliorating Inflammatory Bowel Disease; Oregon State University, Corvallis; Drs. Jan Frederik Stevens, Ryan D. Bradley, and Thomas O. Metz. This project will identify specific gut microbiota that alter the biological signature of xanthohumol, a natural product derived from hops, through metabolic transformations that contribute to normalizing microbial imbalance and inflammation in inflammatory bowel disease. (Grant R01 AT010271)
• Biological Signatures of Blueberry-derived Microbial Metabolites; University of Utah, Salt Lake City; Dr. Anandh Babu Pon Velayutham. This project will explore the molecular mechanisms using multiomics techniques and diabetic laboratory models to determine which blueberry-derived microbial metabolites improve vascular dysfunction during metabolic syndrome using diabetic laboratory models. (Grant R01 AT010247)
• Characterization of Microbiota-derived Polymethoxyflavone Metabolites and their Anti-inflammatory Actions in the Colon; University of Massachusetts Amherst; Dr. Hang Xiao. This project will identify novel microbiota-derived metabolites of polymethoxyflavone (PMF), a compound that comes from citrus; it also seeks to synthesize and test the metabolites in modulating colonic inflammation in animal models, and characterize the transformation of dietary PMFs by specific bacteria into even more effective anti-inflammatory metabolites. (Grant R01 AT010229)