Bifidobacterium Longum R0175 Protects Rats Against D-galactosamine-induced Acute Liver Failure

Objective:The current research focused on the protective efficacy of Bifidobacterium longum R0175 against acute liver failure caused by D-galactosamine(Gal N)in rats and further explored the underlying mechanism.Methods:Sprague-Dawley(SD)rats were randomized into three groups:the negative control(NC)group,the positive control(PC)group,and the B.longum R0175-treated(R0175)group.The rats in the R0175 group were orally administered 1 ml of B.longum R0175solution(3×10~9CFU/ml)per day for seven consecutive days,while the rats in the PC and NC groups were administered an equal amount(1 ml)of sterile normal saline(NS).On the 8th day,a 1.1g/kg(of body weight)dose of D-Gal N was injected intraperitoneally to induce acute liver failure in the rats in the PC and R0175 groups,whereas the rats in the NC group received an equivalent dose of NS.Twenty-four hours later,rat feces along with serum,plasma,liver and ileum tissues were collected for further tests,such as fecal microbiome and metabolome,liver function,histopathological examination of liver and ileum,electron microscopic examination of the ileum,and plasma cytokine.Results:1. Oral gavage of B.longum R0175 markedly reduced the severity of liver pathological damage and improved the impairment of liver function,as evidenced by decreased serum levels of aspartate aminotransferase(AST),total bile acid(TBA),total bilirubin(TBIL)andg-glutamyltransferase(g-GT);2. Administration of B.longum R0175 significantly reduced the plasma concentrations of proinflammatory cytokines(interleukin-1?[IL-1?],tumor necrosis factor-?[TNF-?])and chemokines(granulocyte-macrophage colony-stimulating factor[GM-CSF],monocyte chemoattractant protein-1[MCP-1],growth-regulated oncogene?[GRO?],regulated upon activation normal T cell expressed and secreted factor[RANTES],macrophage inflammatory protein-1?[MIP-1?]);3. Pretreatment with B.longum R0175 partially reversed the gut microbiota dysbiosis in rats with liver injury by increasing the relative abundances of potentially beneficial bacteria,such as Alloprevotella spp.,and decreasing the relative abundances of potentially harmful bacteria,such as Acetatifactor muris,Butyricimonas spp.and Oscillibacter spp.;4. B.longum R0175 administration partially improved the metabolic function of the intestinal microbes,as indicated by the decreased level of lithocholic acid(LCA)in the feces.Conclusion:The results of our research illustrated that supplementation of B.longum R0175exhibited protective effects in rats with acute liver failure,which might be done through affecting the intestinal microbiota and their metabolism,and inhibiting inflammation.Thus,future investigation of the effects and clinical application prospects of B.longum R0175 is warranted.