Moderate consumption of red wine remodels gut microbiota and offers cardiovascular benefits, study shows

Significant changes in gut microbiota were observed in 42 men with coronary artery disease after they took 250 ml of red wine per day for five days a week over a period of three weeks.

By Julia Moióli  |  Agência FAPESP – Moderate consumption of red wine for a few weeks helps remodel the gut microbiota, whose role in the physiology of cardiovascular disease is increasingly recognized by science, according to an article published in The American Journal of Clinical Nutrition.

The article reports on a “Wine Flora Study” involving 42 patients with coronary artery disease. The study was supported by FAPESP via two projects (15/21260-6 and 14/50907-5).

The authors of the article are researchers at the University of São Paulo (USP), the State University of Campinas (UNICAMP) and the University of Brasília (UnB) in Brazil; Verona University in Italy; Harvard University in the United States; and the Austrian Institute of Technology (AIT).

The study consisted of a randomized crossover controlled clinical trial in which each of the participants (men with an average age of 60) underwent two three-week interventions, consuming 250 milliliters of red wine per day for five days a week, and abstaining from alcohol for the same period. A crossover trial is a type of clinical trial in which all participants receive the same two or more treatments, but the order in which they receive them depends on the group to which they are randomly assigned.

The wine was Merlot with an alcohol content of 12.75% produced by the Brazilian Wine Institute (IBRAVIN) specially for the study. Each intervention was preceded by a two-week washout period without consumption of alcohol, fermented foods (such as yogurt, kombucha, soya lecithin, kefir and sauerkraut, for example), prebiotics (including insulin), probiotics, fiber, dairy products, or food polyphenols (such as grapes, cranberries and strawberries).

“In this type of study, the participants act as their own control to eliminate confounding factors [their data is analyzed by comparing participants to themselves before and after each intervention],” said Protasio Lemos da Luz, last author of the article. A professor at USP’s Heart Institute (InCor), he has studied the effects of red wine for over 20 years and has shown experimentally that its consumption by rabbits fed a high-cholesterol diet reduces atherosclerotic plaque formation.

Another strategy used to offset confounders entailed submitting all participants to a controlled diet and having them avoid components of wine such as the polyphenols also present in tea, as well as strawberries and grape juice, as noted earlier.

After each intervention, gut microbiota was analyzed via 16S rRNA high-throughput sequencing, which identifies bacterial species (the 16S mRNA gene is well-conserved in all bacteria). The metabolites present in plasma (plasma metabolome) as a result of the metabolization of chemical compounds and food were analyzed using a technique that combines the separating power of liquid chromatography with the highly sensitive mass analysis capability of mass spectrometry (LC-MS/MS).

One of the metabolites of interest for the researchers is trimethylamine N-oxide (TMAO), which is secreted by gut microbiota from protein-rich food and has been widely reported to correlate with cardiovascular disease, particularly atherosclerosis (cholesterol buildup in arteries).

Remodeling

The researchers found that gut microbiota was significantly remodeled after the period of wine consumption, with bacteria of the genera Parasutterella, Ruminococcaceae, Bacteroides and Prevotella predominating. These microorganisms are vitally important to homeostasis and normal functioning of the human organism generally.

They also observed significant changes in the plasma metabolome after wine consumption, consistent with enhanced redox homeostasis, which maintains a balance between the body's oxidants and antioxidants. Oxidative stress (an excess of oxidants and free radicals over antioxidants) can cause diseases such as atherosclerosis. 

In light of these results, the researchers concluded that gut microbiota modulation can contribute to the presumed cardiovascular benefits of moderate red wine consumption. “Atherosclerosis can be treated with statins – drugs that lower cholesterol and reduce the risk of cardiovascular disease – and by lifestyle changes such as getting more exercise, not smoking, controlling blood pressure and adopting a healthy diet, which can include moderate consumption of wine,” Luz explained.

“We show that moderate wine consumption [common in the South of Brazil as well as France, Italy, Portugal and Spain] can have the kind of beneficial effects on the gut microbiota and plasma metabolome detected in many years of research. Of course, excessive consumption of alcohol – more than 30 grams per day [250 ml in the case of the wine used in the study] – is harmful and associated with an increased risk of death from cancer, accidents and violence.”

More research is needed on the health effects of TMAO, he added, but plasma levels in the study were not different during the periods of wine consumption and abstention. “Although other recently published studies have detected a long-term increase in TMAO as a marker of cardiovascular events, our interpretation is that a three-week period is too short for a significant change to occur,” he said.

The article “A red wine intervention does not modify plasma trimethylamine N-oxide but is associated with broad shifts in the plasma metabolome and gut microbiota composition” is at: academic.oup.com/ajcn/article/116/6/1515/6751899.