Gut Microbiota Dysbiosis and Its Role in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disease in the world; an estimated 30-35% of the world's population is affected, and the prevalence of MASLD has been increasing in recent years.An increasing number of studies have indicated a close relationship between dysbiosis and MASLD.Hence, there is an interest in exploring fatty infiltration as a result of dysbiosis, which includes bacterial composition disturbance, with a profound analysis of preventive and therapeutic factors that impact the occurrence and progression of liver disease.This study aimed to analyze the gut microbiota composition in patients with MASLD, with the potential identification of diagnostic markers and protective factors.Objectives: This study aimed to evaluate the gut microbiota composition in patients with MASLD and MASH, identify potential diagnostic and protective microbial markers, and investigate the role of dysbiosis in the development and progression of the disease.Methods: This study involved 123 subjects divided into two groups (65 MASLD, 18 MASH, and 40 healthy individuals in the control group) with a median age of 49 (23-75) diagnosed with MASH/MASLD based on ultrasound and biochemical tests.The criteria for fatty infiltration included a diffuse increase in the echogenicity of the liver parenchyma, decreased attenuation of the liver, and a ratio between the brightness level of the liver and the right kidney, calculated for the hepato-renal index (HRI) determination.The biochemical evaluation included liver function tests and a lipid profile.Dysbiosis was assessed using a stool bacteriological test and a stool test for dysbiosis.Results: The genus Enterococcus, like Streptococcus, was increased in patients with MASLD/MASH compared with controls.Additionally, uncultured Clostridiales, as well as entero-hemolytic Escherichia coli, were also increased.In contrast, genus Bifidobacterium and Lactobacillaceae were decreased in patients with MASLD/MASH.A significant loss of beneficial bacteria, such as Faecalibacterium, was observed, affecting intestinal barrier function.The diversity of the microbiota was decreased in patients compared with controls.Conclusions: Our study revealed an association between the abundance of Bacteroides in the gut and MASLD/MASH.MASLD developed initially in patients with significant dysbiosis.These results demonstrate that gut microbiota analysis provides prognostic information in addition to classical risk factors for MASLD severity, and strongly suggest that the gut microbiota plays a significant role in the pathogenesis of MASLD.Patients with MASLD should be tested for dysbiosis, and vice versa.It also suggests that correcting the gut microbiome may be beneficial for treating patients with MASLD/MASH.