Grant Abstract: Deciphering polyphenol metabolism by the human gut microbiome

Grant Number: 1R01DK145059-01A1
PI Name: Balskus
Project Title: Deciphering polyphenol metabolism by the human gut microbiome

Abstract: 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.

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