Gut Barrier, Microbial Metabolites, and Immune Homeostasis in Autoimmune Hepatitis: From Molecular Mechanisms to Strategies.

Abstract

Autoimmune hepatitis (AIH) is a chronic immune-mediated inflammatory liver disease characterized by recurring immune-triggered hepatic injury. While scientists have yet to fully elucidate the precise triggers of AIH, contemporary research indicates that both gut microbiota and their metabolic products significantly influence AIH progression. These factors contribute to multiple mechanisms, including compromised intestinal barrier function, altered microbial and metabolite trafficking, and disrupted immune balance, leading to inflammatory responses. This review begins by exploring the intestinal microbial populations and their byproducts linked to AIH. It highlights how disrupted gut flora compromises intestinal immune defenses, enables bacterial migration from the gut to hepatic tissue, and induces liver inflammatory responses. Research validates that metabolic products from microbes, such as short-chain fatty acids (SCFAs), bile acids (BAs), and specific amino acids (glutamine, cysteine, tryptophan, and branched-chain variants, among others), interact with immune cell populations. These interactions, coupled with immune cell modifications, contribute to AIH progression. Our review identifies promising treatment strategies, including the use of probiotic supplementation, engineered prebiotic compounds, microbiota transfer procedures, and specific medications targeting gut microorganisms and their byproducts. These approaches could potentially reduce immune-triggered hepatic damage, offering potential new avenues for AIH management.