# Research progress on the role of gut microbiota dysbiosis in the pathogenesis of immune−mediated liver diseases

## TL;DR

Gut microbiota imbalances contribute to immune-mediated liver diseases through gut-liver axis mechanisms, and targeting the microbiota offers potential therapies.

## Contribution

This paper reviews how gut microbiota dysbiosis contributes to immune-mediated liver diseases and highlights novel therapeutic strategies like FMT and bacteriophages.

## Key findings

- Gut microbiota dysbiosis influences liver diseases via microbial metabolites and immune pathways.
- Specific bacterial species like Veillonella, Enterobacteriaceae, and Klebsiella are associated with different liver diseases.
- Fecal microbiota transplantation and probiotics show promise in treating immune-mediated liver diseases.

## Abstract

Gut microbiota dysbiosis plays a significant role in the pathogenesis of immune-mediated liver diseases (IMLDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC), through multiple gut-liver axis mechanisms. Microbial metabolites such as short-chain fatty acids (SCFAs) and secondary bile acids regulate hepatic immune homeostasis by activating G protein-coupled receptors (GPRs) and the farnesoid X receptor (FXR). Concurrently, disruption of the intestinal barrier integrity allows endotoxins (e.g., lipopolysaccharide) to activate hepatic macrophages via the TLR4/NF-κB pathway, triggering a pro-inflammatory cytokine cascade. Studies indicate an enrichment of Veillonella in AIH patients, while PBC patients display elevated Enterobacteriaceae and reduced Oscillospira spp. PSC is characterized by Klebsiella pneumoniae translocation and Candida albicans toxin-mediated injury. Therapeutic strategies such as fecal microbiota transplantation (FMT), probiotics, prebiotics, and bacteriophages therapy have shown efficacy in clinical settings, underscoring the potential of targeting the gut microbiota for managing IMLDs. Future research should integrate immune cell regulation by gut-derived factors and develop precision therapies based on the gut-liver axis.