High-fat diet-induced colonocyte dysfunction escalates microbiota-derived trimethylamine N-oxide

Woongjae Yoo, Jacob K. Zieba, Nora J. Foegeding, Teresa P. Torres, Catherine D. Shelton, Nicolas G. Shealy, Austin J. Byndloss, Stephanie A. Cevallos, Erik Gertz, Connor R. Tiffany, Julia D. Thomas, Yael Litvak, Henry Nguyen, Erin E. Olsan, Brian J. Bennett, Jeffrey C. Rathmell, Amy S. Major, Andreas J. Bäumler*, Mariana X. Byndloss*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

148 Scopus citations

Abstract

A Western-style, high-fat diet promotes cardiovascular disease, in part because it is rich in choline, which is converted to trimethylamine (TMA) by the gut microbiota. However, whether diet-induced changes in intestinal physiology can alter the metabolic capacity of the microbiota remains unknown. Using a mouse model of diet-induced obesity, we show that chronic exposure to a high-fat diet escalates Escherichia coli choline catabolism by altering intestinal epithelial physiology. A high-fat diet impaired the bioenergetics of mitochondria in the colonic epithelium to increase the luminal bioavailability of oxygen and nitrate, thereby intensifying respiration-dependent choline catabolism of E. coli. In turn, E. coli choline catabolism increased levels of circulating trimethlamine N-oxide, which is a potentially harmful metabolite generated by gut microbiota.

Original languageAmerican English
Pages (from-to)813-818
Number of pages6
JournalScience
Volume373
Issue number6556
DOIs
StatePublished - 13 Aug 2021

Bibliographical note

Publisher Copyright:
Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works

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