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Red meat consumption, gut microbiota and cardiovascular disease
▸ Koeth RA, Wang Z, Levison BS, et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nature Med 2013;19:576–85.
Numerous studies have highlighted the contribution of the gut microbiota to diseases including cancer, inflammatory conditions such as metabolic disorders and also cardiovascular disease (CVD). Mechanistic studies have shown that the colonic microbiota modulates many host functions including lipid accumulation and inflammation, with dietary influence on microbiome composition becoming ever more apparent. However, there is currently little information on the specific mechanisms through which the gut microbiota exerts its effects and also the influence of specific dietary components especially with reference to red meat consumption which is heavily linked to CVD risk within the developed world. Recent studies have shown that microbial processing of dietary choline produces trimethylamine which is further metabolised to the pro-atherogenic species, trimethylamine-N-oxide (TMAO). This recent study from Cleveland, USA examined the gut microbiota-dependent metabolism of L-carnitine to produce TMAO in both rodent and human studies. Using isotope tracer human clinical studies to examine the effects on CVD risk, they demonstrated a mechanistic link between intestinal microbial metabolism of dietary phosphatidylcholine (lecithin) and L-carnitine, derived predominantly from red meat, and coronary heart disease through the production of a pro-atherosclerotic metabolite. This was attributed to suppression of reverse cholesterol transport by the gut microbiota. The authors demonstrate that bacteria belonging to the Firmicutes phylum (specifically within the Clostridiaceae and Peptostreptococcaceae families) were associated with TMAO production. The study highlights the influence that dietary regimes can have on metabolic functioning of the microbiota and clearly demonstrates that dietary influence can be independent of obesity and obesity-associated disorders; although inflammation associated changes are clearly important in CVD.
Caspase-8; a potential novel future therapeutic target for nonalcoholic steatohepatitis
▸ Hatting M, Zhao G, Schumacher F, et al. Hepatocyte caspase-8 is an essential modulator of steatohepatitis in …