Disease of "foie gras": the intestinal flora involved

When the intestinal flora is disrupted, the body does not lead off. In Nature Medicine French researchers from the Institute of Metabolic and Cardiovascular Diseases (Inserm) showed that certain intestinal bacteria played a key role in the development of so-called fatty liver disease, also called hepatic steatosis, in obese people. A potentially serious pathology since it can induce hepatic insufficiency, cirrhosis, or even cancer of the liver.

To reach these conclusions, the team collaborated with Spanish, Italian and English researchers to examine from every angle 800 obese patients. "Our objective is to know if it is possible to diagnose liver disease early, to identify the mechanisms responsible for its development and ultimately to develop therapeutic approaches", described in Figaro Pr Rémy Burcelin , director of research Inserm and responsible for this work.

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Scientists have badyzed liver samples taken from a hundred volunteers and microbial populations populating their intestines by collecting their feces.

Using a mathematical algorithm, the team was able to observe that the alteration of the microbiota largely contributes to the storage of lipids in the liver. "Obese patients with hepatic steatosis have an intestinal microbiota enriched with certain deleterious bacteria that produce fat-promoting substances," says Dr. Burcelin. Among the toxic molecules identified by researchers, phenylacetic acid appears to play a major role in the accumulation of fat in liver cells. This bacterial substance is derived from the digestion of proteins by gut bacteria.

"Phenylacetic acid is a causative agent"

In order to prove the cause-and-effect relationship between intestinal flora, and in particular this bacterial molecule, and hepatic steatosis, the researchers conducted laboratory experiments. First, they transferred microbiota from patients with steatosis to healthy mice. Result: the liver of the animals then began to store in excess the lipids. In parallel, the researchers cultivated liver cells with phenylacetic acid. And again, they notice an accumulation of fat in the cells. "These experiments demonstrate that bacteria can induce steatosis and that phenylacetic acid is a causative agent of this phenomenon," says the researcher.

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Based on these results, Professor Burcelin hopes to develop diagnostic tools for this liver disease. "The alteration of the microbiota and the presence of phenylacetic acid in the blood could serve as biomarkers for identifying patients with steatosis," he says. Better still, these results pave the way for the development of new therapeutic avenues. "To cure a patient, one should start by treating his microbiota. One could for example block the production of phenylacetic acid in bacteria, "he continues. Blocking the action of this molecule or attempting to degrade it before it reaches the liver are also means of action to study.