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High Fat Diet Alters Gut Physiology

iStock-1133727579In a study just published in Science, a mouse-model of diet-induced obesity was used to elucidate possible mechanisms by which a high-fat diet can contribute to atherosclerosis. Animals fed a high-fat diet rich in choline had disruptions in mitochondrial bioenergetics in the cells lining the intestinal tract. The subsequent drop in ATP production, as well as an increase in oxygen and nitrate leakage from colonic epithelial cells, was a driver for changes in the microbiome; specifically, an increase in species such as E. coli that are better adapted to the oxygen-rich environment. Alterations in the microbiome, in turn, led to increased conversion of choline to trimethylamine (TMA), ultimately converted in the liver to trimethylamine-N-oxide (TMAO), well-known for being an independent risk factor for cardiovascular disease.

This study adds to the growing evidence base for the role of diet-induced changes in the microbiome, and how they influence the risk for cardiovascular disease. It helps to broaden our understanding of the mechanisms involved, which include TMA production as well as other microbial metabolites such as short chain fatty acids and secondary bile acids. Indeed, the microbiome is gaining recognition as the chief interface between our cells and the environment, perhaps mediating many of the disease risks typically attributed to “environmental factors,” including hypercholesterolemia. It also helps to pinpoint how interventions, which modify the microbiome, including probiotics and other lifestyle factors, may have the potential to reduce cardiovascular risk.

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