Genome, microbiome and diet linked with atherosclerosis

9 May 2013

New research published in the New England Journal of Medicine reports links between diet, microorganisms that inhabit the gut, and atherogenesis, the development of atherosclerosis.
The microbiome (the normal population of microorganisms that inhabit the human body) is increasingly recognised as playing a potentially important role in the health of different individuals (see previous news). Genetic and environmental factors are also known to influence disease risk and progression. The impressive complexity of such interactions is beautifully illustrated by a recent paper that highlights the involvement of all three factors in the common precursor to coronary artery disease (CAD).
Gut microbes are crucial for normal digestion and metabolism, which are of course also directly affected by diet. Previous studies have suggested a link between intestinal metabolism of choline and CAD via the production of TMAO, the proatherosclerotic metabolite trimethylamine-N-oxide. Choline is derived from dietary phosphatidylcholine, found in foods such as eggs, beef and pork; TMAO is thought to stimulate the production of foam cells, a key precursor of atherosclerosis.
To investigate this link, researchers examined TMAO levels in healthy individuals before and after suppression of the gut microbiome with antibiotics. They confirmed that TMAO levels were significantly reduced during antibiotic use and rose again when it stopped. The researchers also examined levels of TMAO and major cardiovascular events (heart attack, stroke and death) over three years in more than 4,000 people receiving elective coronary angiography. They found that increased TMAO levels were predictive for an increased risk of major cardiovascular events, independent of other risk factors.
The authors conclude that dietary intake of choline should be limited, and hope that their findings may lead to a new therapeutic to reduce CAD risk, perhaps by targeting microbial metabolic pathways that lead to TMAO production.

Comment: Whilst it does not yield any immediate therapeutic breakthrough, this research is important in adding a new example of the importance of the complex interactions between host genome, microbiome and environment in health and disease. Such links may also be relevant to nutritional genomics, examining the impact of diet and genomics on health. 

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