Researchers from the Third Military Medical University in China focused their attention on a compound called trimethylamine-N-oxide (TMAO), which is reportedly a novel and independent risk factor for atherosclerosis. TMAO is produced by specific microorganisms in the gut, which metabolize dietary choline to trimethylamine (TMA), and then liver enzymes complete the conversion to TMAO.
Because of the role of the gut microbiota in the production of TMAO, studies have successfully investigated the potential of antibiotics to attenuate TMAO production and atherosclerosis development. However, the potential side effects and development of antibiotic resistance has stifled efforts.
The new study, published in mBio, an open access journal from The American Society for Microbiology, found that resveratrol, which has potential prebiotic activity, may remodel the gut microbiota to influence the production of bile acid, which in turn decreases TMAO levels.
“These results offer new insights into the mechanisms responsible for resveratrol’s anti-atherosclerosis effects and indicate that the gut microbiota may become an interesting target for pharmacological or dietary interventions to decrease the risk of developing cardiovascular diseases,” wrote researchers from the Third Military Medical University in China.
Resveratrol, a powerful polyphenol and anti-fungal chemical, is often touted as the bioactive compound in grapes and red wine, and has been associated with the so-called 'French Paradox': The phrase was coined in 1992 by Dr Serge Renaud from Bordeaux University to describe the low incidence of heart disease and obesity among the French, despite their relatively high-fat diet and levels of wine consumption.
Because of this link, the majority of studies on resveratrol have focused on the compound’s potential cardiovascular benefits. However, other studies with resveratrol have reported potential anti-cancer effects, anti-inflammatory effects, anti-diabetes potential, energy endurance enhancement, and protection against Alzheimer’s.
The new study adds a potential gut microbiota component to resveratrol’s cardiovascular benefits.
“To the best of our knowledge, we are the first to demonstrate the role of the gut microbiota in resveratrol-induced protection against atherosclerosis,” wrote the researchers.
The Chinese researchers used lab mice with an increased risk of developing atherosclerosis. Animals were fed standard mouse chow with or without supplemental resveratrol (0.4%) for 30 days. At the end of the study, the animals were given doses of choline or TMA.
Results showed that TMAO levels did not increase in animals in the resveratrol group given either choline or TMA, whereas levels did increase in the standard chew-fed control animals. In addition, TMA and TMAO levels were significantly lower in the resveratrol fed animals after the choline dose.
These effects were accompanied by changes in the gut microbiota of the resveratrol-fed animals, said the researchers. Phylum level analysis showed that resveratrol was associated with increases in Bacteroidetes at the expense of Firmicutes. Looking at the bacteria at a genus level showed that resveratrol consumption was associated with increases in the relative abundances of Akkermansia, Bacteroides, Bifidobacterium, and Lactobacillus in the lab animals.
“Our findings suggested that resveratrol likely exerted its primary effects by remodeling gut microbiota,” wrote the researchers. “This might explain the paradox that resveratrol has low bioavailability in humans while exerting noticeable bioactivities.
“These findings provide a new insight into the potential mechanisms responsible for the cardiovascular protective effects of resveratrol and indicate that the gut microbiota may play an important role.”
March/April 2016 Volume 7 Issue 2 e02210-15, doi: 10.1128/mBio.02210-15
“Resveratrol Attenuates Trimethylamine-N-Oxide (TMAO)-Induced Atherosclerosis by Regulating TMAO Synthesis and Bile Acid Metabolism via Remodeling of the Gut Microbiota”
Authors: M-l. Chen, et al.