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

Research output: Contribution to journalArticlepeer-review


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 languageEnglish
Pages (from-to)813-818
Number of pages6
Issue number6556
StatePublished - 13 Aug 2021

All Science Journal Classification (ASJC) codes

  • General


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