The Role And Molecular Mechanism Of S.boulardii-induced Gastrointestinal Microbiota Modulation In Acute Liver Failure Therapy

Objective: Regulation of intestinal microbiota can degrade toxins and reduce toxins absorption,which contribute to reduce liver failure and liver function recovery.However,the involved mechanisms are still unclear.In this study,we aimed to investigate the protective effects of S.boulardii on D-Galactosamine-induced liver failure in mice and the involved themolecular mechanisms.Methods: BALB / C mice were treated as the following: 1)normal control group(group K);2)acute liver failure group(group M);3)S.boulardii control group(group G)4)S.boulardii prevention group(group H);5)S.boulardii therapy group(group I).Acute liver failure mouse model was achieved by the injection of D-galactosamine mice were sacrificed after 36 hours.Then the ALT、AST、TBi L、PTA and histopathological indexes were examined.The diversity and community structure of the oral,gastric,colon,ileum and feces microbiota were studied by sequencing the 16 S r DNA using illumina Hiseq2500.The mice liver was also used for RNA-seq transcriptase sequencing.Results: 1、There were significant differences in the diversity and community structure of the microbiota between the normal control group and the acute liver failure group.The most significant difference was found in the ileum.At the phylum level,we found that D-Galactosamine significantly increased in the relative abundance of Bacteroidetes,and decreased the relative abundance of Firmicutes and Proteobacteria.2、S.boulardii treatment induced significant changes in the gastrointestinal microbial composition,promoted Propionibacteriaceae、Lachnospiraceae.etc growth and inhibited S24-7、Rikenellaceae、TM7.etc growth.3、Genomes pathways analysis showed that S.boulardii treatment had significantly changed several signaling pathway involved in cell apoptosis 、inflammatory 、 autoimmune 、 cholesterol transport.There is little information available for role of TGF-beta signaling of the genomes pathways analysis in liver failure.Our study has found that S.boulardii treatment decreased the expression of Tgfb1 and Smads at m RNA and protein levels.Conclusion: There are significant changes in the diversity and community structure of the microbiota,particularly in ileum,during acute liver failure.S.boulardii treatment reduces liver failure and promotes liver function recovery likely through modulation of the diversity and community structure of the gastrointestinal microbiota,and decreasing the expression of TGF-beta and Smads 2,3 and 8.