[R01] Deciphering polyphenol metabolism by the human gut microbiome
Ente: National Institute of Diabetes and Digestive and Kidney Diseases
Scadenza: 2030-03-31
Importo max: 832.101 EUR
Paese: US
Descrizione
PROJECT SUMMARY
The human gut microbiome mediates many impacts of diet on host health and disease by metabolizing dietary
components. For example, gut microbes extensively transform polyphenols, a prominent class of dietary
compounds abundant in plant-derived foods and beverages. Polyphenol consumption has been strongly linked
to health outcomes, including altered risk for inflammatory bowel disease, cardiovascular disease, cancer, and
diabetes. These links depend on gut microbiome composition, implicating microbial transformations in mediating
effects of polyphenols. However, we lack a mechanistic understanding of gut microbial metabolism of dietary
polyphenols and how this metabolism impacts human health. The long-term goal of this research program is to
decipher how gut microbe-diet interactions influence human biology and disease risk. The overall objective of
this project, which is a critical step toward this goal, is to develop an innovative, interdisciplinary experimental
workflow for deciphering gut microbial metabolism and bioactivities of polyphenols as a prominent class of dietary
compounds. Our preliminary work has established critical experimental frameworks, including genetic tools for
polyphenol-metabolizing gut bacteria, methods for discovering polyphenol metabolic enzymes, and high-
throughput approaches to identify bioactivities and host targets of polyphenol metabolites. Building on this
foundation, our three specific aims will: 1) identify and characterize gut microbial enzymes that mediate
metabolism of multiple classes of polyphenols, 2) elucidate the bioactivities and mechanisms of action of
prominent polyphenol metabolites, and 3) define the in vivo consequences of bacterial polyphenol metabolism
for colitis and gut microbiome composition. Overall, these studies will provide a molecular understanding of gut
microbial polyphenol metabolism and its impacts on human biology, advancing our fundamental understanding
of diet-microbiome interactions and their influence on health and disease.
Istituzione: HARVARD UNIVERSITY
PI: Emily Patricia Balskus, Marco Jost
Progetto: 1R01DK145059-01A1
Settori: National Institute of Diabetes and Digestive and Kidney Diseases
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