Gut bacteria linked to cardiovascular disease

According toWorld Health Organization (WHO). Regular consumption of meat, especially red meat and processed meat, seems to be one of the many factors associated with the onset of these diseases.

Although the physiological mechanisms that explain the association between meat consumption and cardiovascular disease have been extensively studied, they remain controversial. So far, research has rather looked at blood levels of saturated fat and cholesterol to explain the link between animal products and cardiovascular risk. However, a new study published Aug. 1, 2022 in the journal Arteriosclerosis, Thrombosis, and Vascular Biology reveals biochemical links between meat consumption, gut microbiota, and the occurrence of cardiovascular disease.

Researchers have shown for the first time a significant increase in cardiovascular disease by 15% in people who ate meat five times a week or more, compared with people who ate meat only once a week. The study also suggests that L-carnitine, an amino acid highly present in red meat, plays a relatively important role in this increased risk.

L-carnitine and its metabolites are associated with an increased risk

Indeed, by digesting L-carnitine, bacteria in our digestive tract produce metabolites that form trimethylamine N-oxide (TMAO). “After eating animal products, our gut microbes can convert nutrients like L-carnitine into γ-butyrobetaine and crotonobetaine. Each of these can be converted into TMA by our gut bacteria. TMA can then be converted into TMAO by certain liver enzymes” – explains the sciences and achievements Meng Wang, one of the authors of the study.

Scientists have found that higher levels of TMAO and its metabolites explain 8% to 11% of the risk of cardiovascular disease associated with meat consumption. “There have been several studies of TMAO and CV risk, but we didn’t have the full picture. This study is the first to show the complete pathway from red meat to CVD through TMAO,” says Melanie of Science et Avenir. Deschasaux-Tanguy, Research Fellow in Nutritional Epidemiology at INSERM.

Increased inflammation and thrombosis

Therefore, TMAO will be involved in various mechanisms influencing the risk of cardiovascular disease. A recent review of the literature indicates, for example, that this metabolite increases vascular inflammation and the risk of thrombosis and reduces cholesterol transport. “In animal studies, TMAO may promote blood clotting and plaque formation in blood vessels.” Meng Wang.

But for now, the exact mechanisms leading to these effects remain unclear: “We still don’t know if TMAO is just a marker of overall cardiovascular health or a molecule that acts directly. As long as we think it’s both. ”, — admits Melanie DeShaso-Tanguy.

TMA is produced by the microbiota during the digestion of L-carnitine, choline, and other elements found in animal products, especially meat. It is then converted to TMAO in our liver.. It is believed that TMAO is involved in the occurrence of cardiovascular diseases, for example, by increasing vascular inflammation. Credit: Zhang X, Gérard P. Diet-gut microbiota interactions in cardiovascular disease. Comput Struct Biotechnol J. 2022 March 29.

About 4000 participants

To conduct their study, the researchers collected health data from 3,931 Americans originally recruited between 1989 and 1990 and followed up for an average of 12 years. They were all 65 years of age or older, with a median age of about 73 at inclusion.

At that time, all participants had to answer a questionnaire about how often they eat red meat, processed meat, fish, poultry and eggs, as well as their lifestyle. During the dispensary observation, their state of health was assessed, including the presence of cardiovascular diseases.

With all this data, the authors of a recent study were able to measure several meat-related blood biomarkers, including TMAO, using blood samples taken at the start of the study and again in 1996-1997. Researchers have realized that the products of our gut bacteria during digestion alone do not explain the link between consumption of animal products and the risk of cardiovascular disease.

Insulin resistance, a better indicator than TMAO

The authors acknowledge that the relationship between TMAO or its metabolites and consumption of red or processed meat is very modest. They hardly justify their value as a nutritional marker.” comments Didier Chapelo, physician and research lecturer in human nutritional pathophysiology at the Sorbonne Paris-Nord, who is not involved in the study.

There are other factors that may explain this relationship. Beyond these 8-11%, 90% of the association of red meat and cardiovascular disease is not explained by TMAO and its associated metabolites. Glucose, insulin, and CRP, a marker of inflammation, ultimately explain this association between red meat and cardiovascular disease. “It seems that even for meat, insulin resistance remains the main biological parameter that needs to be addressed, and many measures, not only dietary, but also behavioral, such as physical activity, can be used for this. clarifies Didier Chapelo.

The microbiota is complex

We must also take into account the complexity of our microbiota: “There is strong inter-individual variability. Some bacteria will be able to convert L-carnitine to TMA, but not all of them. The varying amounts of these bacteria present in the human body would likely influence the effect of L-carnitine on TMA production and cardiovascular disease risk,” adds Melanie DeShaso-Tanguy.

To limit this mechanism, it would be possible to envisage a treatment that would act on the modulation of the microbiota in order to avoid excess production of TMAO. “But of course we can also have a direct impact on prevention. The best way to reduce the cardiovascular risk associated with meat is, of course, to limit meat consumption,” advises the INSERM researcher.

A few factors to consider

It is also important to note that cardiovascular disease is not solely explained by meat consumption. “Cardiovascular disease is multifactorial: age, smoking, alcohol or lack of physical activity also play a big role,” notes Melanie Deshaso-Tanguy.

Eating fruits and vegetables, getting regular physical activity, getting enough sleep, or even eating a low glycemic index diet all help ensure good cardiovascular health.

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