Microbiome metabolite, TMAO, associated with increased risk of chronic kidney disease and atherosclerosis

Our microbiome is responsible for producing many of the molecules and metabolites that end up in our bloodstream.  Here, these molecules can serve many important therapeutic functions, like in the case of short chained fatty acids (SCFAs).  However, some of these metabolites are beginning to be linked to various diseases.  The best known example of this is microbiome mediated production of trimethylamine-(N)-oxide (TMAO).  TMAO is produced by the microbiome from molecules called carnitine and choline, which come from foods like red meat and eggs.  A lot of literature is now being published that is establishing a connection between TMAO and atherosclerosis, and more recently between TMAO and chronic kidney disease (CKD).  In a new study published last week in the Journal of the American Society of Nephrology, researchers from the University of Kansas assessed the connection between each of these things, TMAO, atherosclerosis, and CKD.

The researchers hypothesized that patients with chronic kidney disease would show increased levels of atherosclerosis because circulating TMAO cannot be cleared from the blood by their injured kidneys.  They measured the degree of CKD and plasma TMAO levels in over 100 patients and confirmed their hypothesis: they noticed a direct relationship between severity of their CKD and circulating TMAO levels.  In addition, the researchers noticed that those people who received kidney transplants had improved TMAO levels, showing that the relationship between CKD and TMAO was most likely due to loss of kidney function.  Finally, the researchers measured biomarkers for atherosclerosis in these patients and correlated the amount of TMAO with the amount of atherosclerosis, even showing that the long term survival of these patients was related to the amount of circulating TMAO levels.

This paper is one of the first to make a connection between circulating TMAO levels and kidney function, which itself is related to atherosclerosis and mortality.  The microbiome is ultimately responsible for the creation of TMAO in the blood, by breaking down things like meats, eggs, and nuts.  It appears that a dietary shift, or a modulation of the microbiome that decreases its ability to perform this transformation should be considered for patients with CKD who are at risk for atherosclerosis.

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