Alcoholic fatty liver disease inhibited the co-expression of Fmo5 and PPAR? to activate the NF-?B signaling pathway, thereby reducing liver injury via inducing gut microbiota disturbance

Abstract Background Alcohol-induced intestinal dysbiosis disrupts and inflammatory responses are essential in the development of alcoholic fatty liver disease (AFLD). Here, we investigated effects Fmo5 on changes enteric microbiome composition a model AFLD dissected pathogenic role AFLD-induced pathology. Methods The expression profile data GSE8006 GSE40334 datasets were downloaded from GEO database. WGCNA approach allowed us to investigate AFLD-correlated module. DEGs used perform KEGG pathway enrichment analyses. Four PPI networks constructed using STRING database visualized Cytoscape software. Cytohubba plug-in was identify hub genes. Western blot immunohistochemistry assays detect protein expression. ELISA assay levels serum cytokines. Lipid droplets cytoplasm observed Oil Red O staining. Apoptosis detected TUNEL flow cytometry analysis. ROS Nuclear translocation NF-?B p65 immunofluorescence Co-immunoprecipitation co-expression PPAR? L02 cells. 16S rDNA sequencing defined bacterial communities mice with AFLD. Results is key DEG closely associated gut microbiota PPAR signaling pathway. Gut function significantly related induced shifts various phyla cecum, including reduction Bacteroidetes increased Firmicutes . cell animal models AFLD, which decreased significantly. Silencing aggravated functions inducing apoptosis response, promoting injury, activating vivo vitro. inhibitor abolished silencing apoptosis, injury. Conclusion Our indicated that involved AFLD-related alleviated response by inhibiting nuclear inhibit