Bifidobacterium animalis ssp. Lactis 420 Mitigates Autoimmune Hepatitis Through Regulating Intestinal Barrier and Liver Immune Cells

Abstract

Autoimmune hepatitis (AIH) is an immune-mediated inflammatory liver disease of uncertain cause. Accumulating evidence shows that gut microbiota and intestinal barrier play significant roles in AIH thus the gut–liver axis has important clinical significance as a potential therapeutic target. In the present study, we found that Bifidobacterium animalis ssp. lactis 420 (B420) significantly alleviated S100-induced experimental autoimmune hepatitis (EAH) and modulated the gut microbiota composition. While the analysis of clinical specimens revealed that the fecal SCFA quantities were decreased in AIH patients, and B420 increased the cecal SCFA quantities in EAH mice. Remarkably, B420 application improved intestinal barrier function through upregulation of tight junction proteins in both vitro and vivo experiments. Moreover, B420 decreased the serum endotoxin level and suppressed the RIP3 signaling pathway of liver macrophages in EAH mice thus regulated the proliferation of Th17 cells. Nevertheless, the inhibition effect of B420 on RIP3 signaling pathway was blunted in vitro studies. Together, our results showed that early intervention with B420 contributed to improve the liver immune homeostasis and liver injury in EAH mice, which might be partly due to the protection of intestinal barrier. Our study suggested the potential efficacy of probiotics application against AIH and the promising therapeutic strategies targeting gut–liver axis for AIH.

Gut Microbiota and Chemical-Induced Acute Liver Injury

“…Mounting evidence showed that the mechanisms of AIH were related to gut dysbiosis (Cai et al, 2017 ; Furukawa et al, 2020 ). Moreover, microbiome restoration therapies, such as probiotics, prebiotics, and fecal microbiota transplantation (FMT), can effectively improve AIH (Allegretti et al, 2019 ; Zhang et al, 2020 ). The study of gut microbiota will provide new insights into the mechanism of AIH.…”

The Microbiome in Autoimmune Liver Diseases: Metagenomic and Metabolomic Changes

“…Furthermore, patients with lower Bifidobacterium failed to achieve remission (Lv et al, 2020). Zhang et al (2020) reported that Bifidobacterium lactis 420 have beneficial functions in alleviating experimental autoimmune hepatitis. It suggested probiotics supplements may help to treat AIH in the future.…”

Protective Property of Scutellarin Against Liver Injury Induced by Carbon Tetrachloride in Mice

“…FGF19/FGF15 inhibits CYP7A1 expression in the liver and then decreases bile acid synthesis ( Wahlström et al, 2016 ). Moreover, all-trans retinoic acid involved in retinol metabolism can significantly activate hepatic FXR, contributing to the inhibition of CYP7A1, thereby decreasing the synthesis of bile acid ( Zhang et al, 2020 ). In this study, we found an increased deoxycholic acid (DCA) level in the feces and decreased all-trans retinoic acid levels in the liver in the CCl 4 -treated group, which was improved by SCU treatment.…”