Role of the gut microbiota in liver diseases | Role of the gut microbiota in liver diseases: Attestation from microbiota transplants in germfree animal models

International audience

English. The human intestine is home to a complex bacterial community known as the gut microbiota. This microbiota performs functions that are essential for maintaining our health, and has been shown to influence the host's physiology and metabolism. As a result, dysregulation of this intestinal microbiota, known as dysbiosis, could be implicated in the development of various diseases. However, studies analysing the microbiota rarely assess causality, which can be demonstrated by using germ-free (GF) animals and transplanting microbiota. Using these strategies, it has been shown that the intestinal microbiota may play a causal role in the development of obesity and associated metabolic disorders, particularly liver diseases, including Metabolic dysfunction–associated steatotic liver disease (MASLD) and Alcoholic liver disease (ALD). Indeed, by transplanting the gut microbiota from mice with or without MASLD to GF mice, we showed that the propensity to develop MASLD features including hyperglycaemia or steatosis is transmissible by the gut microbiota. Regarding ALD, we first showed that a specific dysbiosis is present in alcoholic patients with a severe alcoholic hepatitis. GF mice colonized with the gut microbiota from a patient with severe alcoholic hepatitis (AH) developed more severe liver inflammation and higher liver necrosis, than GF mice colonized with the gut microbiota from an alcoholic patient without AH.In conclusion, we demonstrated that the individual susceptibility to liver diseases is driven, at least partly, by differences in intestinal microbiota composition. Our findings open new avenues for diagnostic procedures based on personalised medicine by the identification of patients at high risk of developing liver diseases. They also open new possibilities for liver diseases prevention and treatment through intestinal microbiota manipulation.