Red Meat Increases Cardiovascular Risk via Raised TMAO Production by the Gut Microbiome
More research into aging and the gut microbiome is taking place these days. A greater investment into this line of research will, as illustrated here, likely lead to a greater knowledge of the mechanisms underlying the known correlations between diet and age-related conditions. That red meat consumption increases cardiovascular risk is quite well established from epidemiological data, and here researchers outline their view of why this happens. One might contrast this with the present consensus, which is that red meat consumption increases lipid levels in the bloodstream, thereby accelerating atherosclerosis and consequent cardiovascular mortality.
In a previous series of studies, researchers found that a byproduct that forms when gut bacteria digest certain nutrients abundant in red meat and other animal products - called TMAO (trimethylamine N-oxide) - increases the risk of heart disease and stroke. The latest findings offer a more comprehensive understanding of the two-step process by which gut microbes convert the nutrient carnitine into TMAO, an atherosclerosis- and blood clot-promoting molecule, following the ingestion of a red meat-rich diet.
Dietary carnitine is converted into TMAO in the gut through a two-step, two microbe process. An intermediary metabolite in this process is a molecule called γBB (gamma-butyrobetaine). Multiple gut microbes can convert dietary carnitine to γBB, but very few can transform the molecule to TMA, the precursor to TMAO. "In omnivores, Emergencia timonensis is the primary human gut microbe involved in the transformation of γBB to TMA/TMAO. Conversely, long-term vegetarians and vegans have very low levels of this microbe in their gut and therefore have minimal to no capacity to convert carnitine into TMAO."
The researchers studied the relationship between fasting plasma γBB levels and disease outcomes using samples and clinical data collected from nearly 3,000 patients. Higher γBB levels were associated with cardiovascular disease and major adverse events including death, non-fatal heart attack or stroke. To understand the mechanistic link between γBB and the observed outcomes in patients, the researchers studied fecal samples collected from mice and patients, as well as preclinical models of arterial injury. They found that introducing E. timonensis completes the transformation of carnitine to TMAO, elevates TMAO levels, and enhances blot clot potential.