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

94 Scopus citations


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
Issue number6556
StatePublished - 13 Aug 2021

Bibliographical note

Funding Information:
W.Y. was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) by the Ministry of Education 2020R1A6A3A03037326. Y.L. was supported by Vaadia-BARD Postdoctoral Fellowship FI-505-2014. E.E.O. was supported by Public Health Service Grant TR001861. C.S. was supported by the Dorothy Beryl and Theodore Roe Austin Pathology Research Fund and T32AI112541. N.J.F. was supported by T32DK007673-07. N.G.S. was supported by T32ES007028-46. E.G. and B.J.B. were supported by the U.S. Department of Agriculture (USDA) Project 2032-51530-025-00D. Work in A.J.B.'s laboratory was supported by USDA/NIFA award 2015-67015-22930; by Crohn's and Colitis Foundation of America Senior Investigator Award 650976; and by Public Health Service Grants AI044170, AI096528, AI112445, AI112949, AI146432, and AI153069. Work in M.X.B.'s laboratory was supported by V Scholar grant V2020-013 from The V Foundation for Cancer Research, Vanderbilt Digestive Disease Pilot and Feasibility grant P30 058404, ACS Institutional Research Grant IRG-19-139-59, VICC GI SPORE grant P50CA236733, United States-Israel Binational Science Foundation grant 2019136, and Vanderbilt Institute for Clinical and Translational Research Grant VR53102 and VR54267.

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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