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

Science (New York, N.Y.) 2021 Aug 13

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

Citation

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. High-fat diet-induced colonocyte dysfunction escalates microbiota-derived trimethylamine N-oxide. Science (New York, N.Y.). 2021 Aug 13;373(6556):813-818