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Intestinal bacteria cause worsening of fatty liver disease, according to a study by Inserm in partnership with researchers from London, Rome and Girona and published in Nature Medicine . [19659002] NASH . Also known as NASH (non-alcoholic steatohepatitis) or fatty liver of its medical name, fatty liver disease affects 70 to 80% of people suffering from obesity and diabetes. This accumulation of fats in the liver leads to liver failure, resulting in a risk of cancer development and a reduced ability to filter environmental and dietary toxins. There is no medicine to treat NASH, apart from a strict diet or, in the most severe cases, a liver transplant.
The "big data" applied to the microbiota: more than 3 million genes badyzed
Faced with this therapeutic stalemate, the European consortium (FLORINASH) of French, Italian and English researchers decided to examine the role of intestinal bacteria, also called intestinal microbiota, in NASH. Indeed, previous studies have already explained the harmful role of this microbiota in the development of obesity and diabetes.
The researchers therefore created and collected data from two large cohorts of 800 men and women suffering from 'obesity. Among those who had NASH, a smaller subset of obese women (approximately 100) were subjected to molecular badyzes based on liver biopsies, urine and plasma specimens, and collection of saddles. The large database thus constituted was badyzed by the so-called "big data" approach, that is to say by algorithms developed by the researchers to identify logical links between the data. " We wanted to see if we could identify, step by step, from the microbiota, the succession of mechanisms responsible for liver disease ", explains in a statement Rémy Burcelin, director of research at Inserm, coordinator of these works. Thus more than 3 million bacterial genes have been screened by algorithms!
FOIE GRAS WITHOUT GAVAGE . Remy Burcelin, coordinator of this research, is also at the origin of a method using the microbiota to produce duck foie gras without gavage.
The microbiota " orchestra " the NASH in three ways
The researchers then come to two conclusions. First, as the disease progresses, the diversity of microbial genes found decreases, suggesting a reduction in the composition of the microbiota even before the first symptoms appear. Secondly, one of the specific compounds of the microbiota, called phenylacetic acid, promotes the accumulation of fats in the liver.
To verify that there is indeed a cause and effect link, the researchers have introduced a microbiota badociated with the NASH to healthy mice. The level of triglycerides (fats) then increased drastically in the liver of these mice, and the genes involved in lipid metabolism were strongly activated. Similarly, the administration of phenylacetic acid to the mice triggered the accumulation of fats in their liver. Conclusions of the researchers: according to them, the microbiota " orchestrates three possibly complementary contributions " to the NASH in the obesity. First, the decline in the diversity of bacterial species present in the microbiota may be a factor driving NASH and an increase in the production of certain compounds. Then, among these compounds is in particular phenylacetic acid and other molecules promoting the accumulation of lipids in the liver. Finally, the microbiota could induce an inflammation of the liver cells that poison the disease.
According to the team, it would be possible in the long run, by manipulating microbiota bacteria, to prevent obesity-related liver complications. . The idea is also to be able to lead to the development of a new generation of probiotics and a pharmacological strategy interfering with the bacterial mechanisms responsible for liver disease.
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