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. High-fat diet-induced colonocyte dysfunction escalates microbiota-derived trimethylamine -oxide. Science (New York, N.Y.). 2021 Dec 13;373(373). 813-818. PMID: 34385401 [PubMed]
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 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 In turn, choline catabolism increased levels of circulating trimethlamine -oxide, which is a potentially harmful metabolite generated by gut microbiota.