Bifidobacterium longum R0175 Protects Rats against d-Galactosamine-Induced Acute Liver Failure.

Kaicen Wang,Liya Yang,Jianzhong Ye,Jingjing Wu,Xianwan Jiang,Wenrui Wu,Qing Wang,Huiyong Jiang,Yanmeng Lu,Qiangqiang Wang,Jian Shen,Lanjuan Li,Longxian Lv,Yating Li,Jiaojiao Xie,Xiaoyuan Bian,Ren Yan,Maria L Marco

doi:10.1128/msphere.00791-19

Abstract

Acute liver failure is a severe liver disorder that poses considerable global challenges. Previous studies on Bifidobacterium longum R0175 have mainly focused on its psychotropic functions. The current research focused on the protective efficacy of B. longum R0175 against acute liver failure caused by d-galactosamine (d-GalN) in rats and further tested the hypothesis that B. longum R0175 exerted liver-protective effects by affecting the intestinal microbiota and fecal metabolites and by inhibiting inflammation. We found that oral gavage of B. longum R0175 markedly reduced the severity of liver injury in d-GalN-treated rats, as evidenced by decreased serum levels of aspartate aminotransferase (AST) and total bile acids (TBAs) (P < 0.05). Moreover, the plasma concentrations of proinflammatory cytokines (interleukin 1β [IL-1β] and tumor necrosis factor-α [TNF-α]) and chemokines (granulocyte-macrophage colony-stimulating factor [GM-CSF], macrophage chemoattractant protein 1 [MCP-1], chemokine [C-X-C motif] ligand 1 [CXCL1], chemokine [C-C motif] ligand 5 [CCL5], and macrophage inflammatory protein-1α [MIP-1α]) were also markedly reduced (P < 0.05). 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. Furthermore, B. longum R0175 administration partially improved the metabolic function of the intestinal microbes, as indicated by the decreased level of lithocholic acid found in the feces.IMPORTANCE Our research investigated the protective and preventive roles of B. longum R0175 in a rat model of acute liver failure. The results illustrated that this probiotic strain exhibited protective effects in rats with acute liver failure. Thus, B. longum R0175 showed clinical application prospects that required further exploration.

Highlights

Acute liver failure is a severe liver disorder that poses considerable global challenges
D-GalN injection sharply increased the serum levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total bile acids (TBAs), gamma-glutamyltransferase (GGT), glycylproline dipeptidyl aminopeptidase (GPDA), and total bilirubin (TBil) in the PC group compared with the NC group
The relative abundance of P. clara was negatively correlated with the levels of IL-1␤, TNF-␣, chemokines (GM-CSF, CXCL1, MIP-1␣, CCL5, and macrophage chemoattractant protein 1 (MCP-1)), ALT, AST, and TBAs and with histological activity index (HAI) scores

Summary

Introduction

Acute liver failure is a severe liver disorder that poses considerable global challenges. We focused on the protective effects of B. longum R0175 against D-galactosamine (D-GalN)-induced acute liver failure in rats. We performed correlation analyses of the important indexes, including representative microbes, metabolic biomarkers, liver injury parameters, and inflammatory cytokines, among the three groups (Fig. 7).

Results

Conclusion