The study focused on the mechanisms responsible for resveratrol’s anti-atherosclerosis effects via the microbiota.
Cardiovascular disease remains the leading cause of death in industrialised societies within Europe with the incidence also growing in developing countries.
Statistics presented over the last 2 years report that CVD is also the most common cause of death among Europeans and despite steady decreases in CVD mortality rates across the continent, more than four million Europeans die of CVD every year.
An increasing body of research has pinpointed the gut microbiome as central to the build-up of artery plaque.
Equally, research has identified resveratrol - a polyphenol found in red wine – as having antioxidant properties that protect against conditions such as heart disease. Despite the quantity of studies its mechanism of action remains unclear.
Gut microbiome’s role
Scientists from the Research Center for Nutrition and Food Safety, in Chongqing, China, used mice models to investigate whether resveratrol’s protective effect against atherosclerosis was linked to gut microbiome changes.
Here trimethylamine (TMA) and trimethylamine-N-oxide (TMAO) levels were measured at 0, 1, 2, 4, 6 and 8 hours after administration of a single dose of the nutrient choline (400 mg/kg of body weight) or TMA (40 mg/kg) in mice. Choline has been strongly linked in the development of atherosclerosis.
They found that resveratrol reduced levels of TMAO, another contributor to the development of atherosclerosis. They found that resveratrol inhibited TMA production. TMA is necessary for the production of TMAO.
"We found that resveratrol can remodel the gut microbiota, inhibiting the growth of Prevotella, and increasing the relative abundance of Bacteroides, Lactobacillus, Bifidobacterium, and Akkermansia in mice," said Dr Man-tian Mi, principal investigator of the study.
"Resveratrol reduces TMAO levels by inhibiting the gut microbial TMA formation via remodelling gut microbiota."
According to Mi, the natural origins of resveratrol means there are no side effects associated with pharmacological therapies for cardiovascular disease.
Resveratrol may also be a good candidate as a prebiotic and could be used to promote the growth of beneficial bacterium offering a wealth of health benefits to the host.
Previous TMAO & resveratrol studies
Previous studies have identified TMAO as inducing atherosclerosis by affecting cholesterol metabolism through inhibiting hepatic bile acid synthesis. Recently, the gut microbiota has been implicated in hepatic bile acid synthesis
Investigations into resveratrol’s properties have confirmed that a polyphenol-rich cranberry extract combined with metformin weakened diet-induced metabolic syndrome in mice in a gut microbiota-dependent manner.
Resveratrol’s consumption has also been found to control the growth of certain gut microbiota in vivo, including the growth of Bacteroides, Lactobacillus, and Bifidobacterium.
Given the strong relationships between TMAO levels and gut microbiota, the researchers hypothesised that resveratrol weakened TMAO-induced atherosclerosis by regulating TMAO synthesis and via the gut microbiota.
“These results open a new avenue of research regarding the potential cardiovascular protective effects of resveratrol and indicate that the gut microbiota may become an interesting target for pharmacological or dietary interventions to decrease the risk of developing CVD,” the authors concluded.
Published online ahead of print, 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: Ming-liang Chen, Long Yi, Yong Zhang, Xi Zhou, Li Ran, Jining Yang, Jun-dong Zhu, Qian-yong Zhang, Man-tian Mi