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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Yoo, W; Zieba, JK; Foegeding, NJ; Torres, TP; Shelton, CD; Shealy, NG; Byndloss, AJ; Cevallos, SA; Gertz, E; Tiffany, CR; Thomas, JD; Litvak, Y; Nguyen, H; Olsan, EE; Bennett, BJ; Rathmell, JC; Major, AS; Bäumler, AJ; Byndloss, MX

Published Date

  • August 13, 2021

Published In

Volume / Issue

  • 373 / 6556

Start / End Page

  • 813 - 818

PubMed ID

  • 34385401

Pubmed Central ID

  • PMC8506909

Electronic International Standard Serial Number (EISSN)

  • 1095-9203

Digital Object Identifier (DOI)

  • 10.1126/science.aba3683


  • eng

Conference Location

  • United States