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