A new charge weighs on the gut that ends up in the dock as an additional cardiovascular risk factor: Lipopolysaccharide (LPS), an endotoxin from the wall of intestinal bacteria, which can reach arterial vessels, causing inflammation and thrombosis.

This was revealed by a series of research carried out by a team from Sapienza University, coordinated by Professor Emeritus Francesco Violi, and published in the prestigious journal Nature Reviews-Cardiology. These findings provide breakthroughs in understanding the factors that inflame arteries and promote the onset of a heart attack.

The study highlighted that, for reasons related to a functional disorder of the intestinal wall, lipopolysaccharide (LPS) could cross the wall itself and reach the arteries promoting inflammation to the point of thrombosis. The results showed that LPS was present in carotid arteries affected by severe atherosclerotic damage in subjects at high risk of stroke and in thrombi taken from the coronary arteries of patients who had undergone myocardial infarction.

Finally, in more than 900 patients at risk of cardiovascular events, the researchers determined that blood measurement of LPS allowed them to identify patients at increased risk of heart attack and stroke, providing a new tool to study atherosclerosis and its serious cardiovascular complications.

Together these data include the gut among cardiovascular risk factors and suggest that lowering intestinal permeability can reduce the danger of cardiovascular disease.

The main causes that can lead to increased intestinal permeability, and thus increased LPS in the blood, such as a particularly fatty diet, alcohol, prolonged use of anti-inflammatory drugs, infections and systemic inflammation, as well as advanced age, are focused on in the research.

"Future remedies," says Francesco Violi, "are to be sought first and foremost in adequate prophylaxis, favouring the Mediterranean diet and reducing alcohol intake. Some nutrients such as legumes and extra virgin olive oil," Violi points out, "have a protective effect as they increase 'good' bacterial species and intestinal permeability".

The main developments in this research are moving in two directions: the imminent publication of the results of a local intestinal antibiotic, which is currently in trials, and studies of potential ways to detoxify LPS.

"Our hope," concludes Francesco Violi, "is that future research can explore both the possibility of acting on the microbiota to reduce the pathogenicity of LPS and delve through genetic engineering into strategies to neutralize it when it has already crossed the intestinal wall."

References:

Gut-derived low-grade endotoxaemia, atherothrombosis and cardiovascular disease – Francesco Violi, Vittoria Cammisotto, Simona Bartimoccia, Pasquale Pignatelli, Roberto Carnevale, Cristina Nocella – Nature Reviews Cardiology (2022) https://doi.org/10.1038/s41569-022-00737-2

Further Information

Francesco Violi
Department of Clinical Internal, Anaesthesiological and Cardiovascular Sciences
francesco.violi@uniroma1.it