Intestinal microbiome and permeability in patients with autoimmune hepatitis

Abstract Autoimmune hepatitis (AIH) is a severe inflammatory liver disease. The underlying mechanisms remain unclear, but recent studies provided new perspectives on altered intestinal microbiome and permeability in AIH animal models and patients, highlighting gut-liver crosstalk in the pathogenesis of AIH. Transgenic AIH mice carrying HLA-DR3 showed reduced diversity and total load of gut microbiota. Germ-free mice are resistant to concanavalin A-induced liver injury, whereas enterogenouss antigens induce the activation of natural killer T cells participating in concanavalin A-induced liver injury, supporting the close relationship between microbiota and AIH. Moreover, ‘molecular mimicry’ provides a plausible interpretation of the immune reactions between microorganic antigens and liver autoantigens, for instance, cytochrome P4502D6, the target of cross-reactivity between virus and self. Nevertheless, direct evidence for the intestinal microbiome and permeability in AIH is still limited. The relationship between AIH susceptibilities and an intestinal microbiome shaped by drugs, diets or genes needs further study.