The gut microbiota in metabolic dysfunction-associated fatty liver disease

Numerous studies show a modification of the gut microbiota in patients with obesity or diabetes. Fecal transplant experiments have demonstrated the involvement of the gut microbiota in insulin resistance, thus allowing these changes to be called "dysbiosis". In the same vein, animal studies have shown a causal role of gut microbiota in liver steatosis whereas the human situation is less clear. Patients with MAFLD also have a modification in their gut microbiota composition but the changes are not fully characterized. The absence of consensus on a precise signature is probably due to heterogeneous disease, possible concomitant medications and different selection or evaluation criteria. The most consistent changes were increased relative abundance of Proteobacteria, Enterobacteriaceae and Escherichia species and decreased abundance of Coprococcus and Eubacterium. Possible mechanisms linking the microbiota and MAFLD are increased intestinal permeability with translocation of microbial products into the portal circulation, but also changes in the bile acids and production of microbial metabolites such as ethanol, short chain fatty acids and aromatic amino acids able to modulate liver metabolism and inflammation. This gut-liver axis must also be analysed taking into account other tissues which may participate in the metabolic context, namely adipose tissue and muscle. Several interventional studies exist that attempt to modulate liver disease by administering probiotics, prebiotics, synbiotics or antibiotics. The results on liver disease are variable. Indirect markers of improvement are sometimes noted but an impact on histology has not been demonstrated on a large scale. Due to the small size of the series, these treatments are not currently recommended. Interestingly, it should be noted that the individual response to an intervention is variable. Certain microbial signatures seem to respond particularly well to prebiotic administration for example. Precise characterization of broad microbial changes (bacteria, viruses, fungi) in MAFLD patients according to each disease stage is therefore necessary, as well as adequate intervention studies in targeted patients in order to unravel the relevance of microbiota intervention in the management MAFLD