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Drugs for your bugs

Nature Reviews Microbiology volume 14, page 63 (2016)Cite this article

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The generation of TMAO is a two-step process that involves both the gut microbiota and the host: following ingestion of TMA-containing foods (such as those rich in choline, phosphatidylcholine and carnitine), microbial TMA lyases generate TMA, which is then processed by host liver enzymes into TMAO. Therefore, Wang et al. sought to identify inhibitors of microbial TMA lyases as potential therapeutics for atherosclerosis. They screened structural analogues of choline and found that 3,3-dimethyl-1-butanol (DMB) reduced the production of TMA from choline in Proteus mirabilis and in recombinant Escherichia coli cells expressing the CutC–CutD enzymatic complex of P. mirabilis that is responsible for the production of TMA. Furthermore, microorganisms from mouse caecal contents and human faeces could produce TMA when grown in the presence of choline, phosphatidylcholine or carnitine, and TMA production from all of these substrates was inhibited in the presence of DMB. Importantly, DMB was able to inhibit the production of TMA by the commensals P. mirabilis, Proteus penneri or Escherichia fergusonii in a rich nutrient broth without affecting the growth of these bacteria, which may reduce the development of drug-resistant bacterial mutants.

DMB treatment reduced ... the development of atherosclerotic plaques

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References

  1. Wang, Z. et al. Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell 163, 1585–1595 (2015)

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  1. Cláudio Nunes-Alves
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Sommer, F. & Bäckhed, F. The gut microbiota — masters of host development and physiology. Nat. Rev. Microbiol. 11, 227–238 (2013)

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Nunes-Alves, C. Drugs for your bugs. Nat Rev Microbiol 14, 63 (2016). https://doi.org/10.1038/nrmicro.2015.23

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