Resveratrol Reduces Atherosclerosis by Altering Gut Microbiota

by | Jul 15, 2019 | 2016, Cardiovascular Health, Resveratrol

Written by Joyce Smith, BS. Using a mouse model, researchers demonstrate that resveratrol decreases TMAO-induced atherosclerosis by regulating TMAO synthesis and bile acid metabolism via altering gut microbiota.

MIcrobiome - probioticsThe incidence of cardiovascular diseases (CVDs), such as atherosclerosis (AS), is increasing globally and becoming a costly public health issue 1. Plasma trimethylamine-N-oxide (TMAO), a choline metabolite, is considered a novel and independent risk factor for promoting AS 2,3.  Koeth, in 2013, discovered that our gut microbiota are responsible for the generation of TMAO 4. Gut bacteria first metabolize dietary choline to trimethylamine (TMA), which is then transported via the portal vein to the liver where it is converted by a family of hepatic flavin monooxxgenases (FMOs) into TMAO 4.  Antibiotics have been shown to decrease the microbiota-controlled TMAO synthesis by blocking the pathway of L-carnitine to TMA; however, they have a tendency to develop resistance which limits their use 4. However, Resveratrol (RSV), a polyphenol prevalent in grapes and berries, has been shown to be beneficial in treating metabolic diseases including heart disease 5 and although phenolic phytochemicals have low bioavailability, a growing body of evidence supports the hypothesis that they may be acting primarily through remodeling of the gut microbiota. 5-7. Given the close association among TMAO levels, gut microbiota, bile acid metabolism, and AS, Chen et al hypothesized that RSV could attenuate TMAO-induced AS by regulating TMAO synthesis and bile acid metabolism via gut microbiota. To verify this hypothesis, they examined the effects of RSV on TMAO induced AS, gut microbiota, TMAO synthesis, and BA metabolism in C57BL/6J and ApoE -/- mice.8

Results demonstrated that the protective effect of resveratrol against atherosclerosis was indeed linked to changes in the gut microbiota of mice.  RSV decreased TMAO- induced atherosclerosis by decreasing TMA production and subsequent TMAO synthesis, and by increasing bile acid deconjugation and fecal excretion via remodeling the composition of gut microbiota. Specifically, RSV modulated gut microbiota composition through increasing the Bacteroidetes-to-Firmicutes ratios, inhibiting the growth of Prevotella, and increasing the relative abundance of Bacteroides Lactobacillus, Bifidobacterium, and Akkermansia in mice. In fact, treatment with RSV resulted in an increase in the abundance of Bacteroidetes (from 20.6% to 34.0%) at the expense of Firmicutes (from 60.1% to 50.1%) in choline-treated ApoE mice. Furthermore, the potential involvement of the enterohepatic FXR-FGF15 axis was also investigated. Chen et al showed, for the first time, that RSV attenuated TMAO-induced AS by decreasing TMAO levels and increasing hepatic BA neosynthesis via gut microbiota remodeling and that RSV-induced BA neosynthesis was partially mediated through the enterohepatic FXR-FGF15 axis.8

These results offer new insights into the mechanisms responsible for RSV’s anti-AS effects and validates that RSV reduced TMAO levels by inhibiting gut microbial TMA formation via remodeling of gut microbiota. Additional research replicating these results in humans is warranted to further investigate the role of this natural side effect-free polyphenol as a potential therapy for the prevention and treatment of cardiovascular disease.

Source: Chen M-L, Yi L, Zhang Y, Zhou X, Ran L, Yang J, Zhu J-D, Zhang Q-Y, Mi M-T. 2016. Resveratrol attenuates trimethylamine-N-oxide (TMAO)-induced atherosclerosis by regulating TMAO synthesis and bile acid metabolism via remodeling of the gut microbiota. mBio 7(2):e02210-15. doi:10.1128/mBio.02210-15.

© 2016 Chen et al. This is an open-access article distributed under the terms of the  Creative Commons Attribution 4.0 International license.

Click here to read the full text study.

Posted July 15, 2019.

Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from  the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.

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