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

Gut bugs and systemic disease risk What people eat has an immediate selective effect on the microbial populations resident in the gut. A high-fat diet is associated with the occurrence of microbes that catabolize choline and the accumulation of trimethylamineN -oxide (TMAO) in the bloodstream, a contributing factor for heart disease. Yooet al . explored the microbial organisms and pathways that convert choline into TMAO in mice. Although gene clusters for choline metabolism are found widely among the microbiota, it is only the facultative anaerobes that become abundant in hosts on a high-fat diet. A high-fat diet impairs mitochondrial uptake of oxygen into host enterocytes and elevates nitrate in the mucus, which in turn weakens healthy anaerobic gut function. Facultative anaerobes such as the pathobiontEscherichia coli become dominant, which leads to an overall increase in the amount of choline catabolized into the precursor for TMAO. Whether this pathway plays a role in heart disease remains unclear. —CA