Drugging the microbiome to decrease atherslcerosis

TMAO is sometimes found in fish.

TMAO is sometimes found in fish.

Trimethylamine N-oxide is a metabolite produced by the microbiome from foods such as red meat and fish.  This metabolite has been independently linked to atherosclerosis, among a host of other diseases.  Researchers at the Cleveland Clinic have been investigating the relationship between the microbiome and this molecule for many years, and we have written about a few of their publications previously.  (Click the TMAO tag below to learn more.)  Most recently, they have researched various compounds that could possibly decrease the production of TMAO by the microbiome.  Last week they published the results of this study in the journal Cell.

The researchers identified a molecule, 3,3-dimethyl-1-butanol (DMB), which inhibited the production of TMAO by gut bacteria.  DMB is a natural product that is commonly found in balsamic vinegar and olive oil.  This molecule was able to shift the microbiome towards bacteria that did not produce TMAO, and importantly, it did not strictly act as an antibiotic and broadly decrease the abundance of microbiome bacteria.  The scientists tested this molecule in mice and showed that it decreased the plasma levels of TMAO in mice that ingested choline.  Moreover, the mice that received DMB had less arterial plaque (i.e. less atherosclerosis).  In addition, the DMB did not appear to have any toxic effects on the mice. 

These researchers hope that the DMB or other agents that lower TMAO levels could possibly be used as therapeutics.   Beyond atherosclerosis, TMAO has been implicated in a number of diseases, ranging from certain cancers to inflammatory diseases.  These diseases are complex though, and their etiologies are not completely understood, so it remains to be seen if this microbiome approach will be successful.  In the mean time, a little less red meat and a little more balsamic vinegar probably won’t hurt.  

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