Intestinal homeostasis in autoimmune liver diseases

Abstract

Intestinal homeostasis depends on complex interactions between the gut microbiota and host immune system. Emerging evidence indicates that the intestinal microbiota is a key player in autoimmune liver disease (AILD). Autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, and IgG4-related sclerosing cholangitis have been linked to gut dysbiosis. Diverse mechanisms contribute to disturbances in intestinal homeostasis in AILD. Bacterial translocation and molecular mimicry can lead to hepatic inflammation and immune activation. Additionally, the gut and liver are continuously exposed to microbial metabolic products, mediating variable effects on liver immune pathologies. Importantly, microbiota-specific or associated immune responses, either hepatic or systemic, are abnormal in AILD. Comprehensive knowledge about host-microbiota interactions, included but not limited to this review, facilitates novel clinical practice from a microbiome-based perspective. However, many challenges and controversies remain in the microbiota field of AILD, and there is an urgent need for future investigations.

Incorporating the Molecular Mimicry of Environmental Antigens into the Causality of Autoimmune Hepatitis

“…The dual reactivity is dependent on an intact intestinal microbiome in a mouse model of inflammatory bowel disease [ 229 ]. The absence of this dual reactivity in germ-free animals supports the premise that gut-derived antigens can escape the intestine and trigger an antibody response that is disease-related [ 229 – 231 ]. The high prevalence and high titers of atypical pANCA in some studies of type 1 autoimmune hepatitis [ 218 , 223 ] compel this consideration, albeit the antibody production may not translate into a pathogenic immune response.…”

“…Gut-derived homologous peptides must translocate from the intestine to extra-intestinal sites to generate pathogenic, cross-reactive, T and B cell responses [ 188 ]. The genetic and biological factors that contribute to these responses must be clarified in autoimmune hepatitis [ 231 ] (Table 3 ). The enteric milieu of short chain fatty acids [ 198 – 201 ], LSP [ 197 ], glycolipids [ 217 ], and bile acids [ 189 , 209 ] must be characterized to define the conditions for increased intestinal permeability.…”

“…The feasible management strategies for pathogenic molecular mimicry include life-style changes [ 277 ], dietary adjustments or supplements [ 204 , 211 , 231 , 277 – 280 ], improved vaccine production [ 161 ], and targeted manipulation of the intestinal microbiome [ 44 , 47 , 135 , 214 , 231 , 281 ] (Table 3 ). Diets emphasizing fiber [ 211 ] and favoring the intestinal production of short chain fatty acids [ 280 ] and butyrate [ 203 – 205 , 211 ] may preserve or strengthen the intestinal mucosal barrier.…”

Editorial: Hepatic immune response underlying liver cirrhosis and portal hypertension

“…Hepatic immunity is affected not only by liver damage but also by other organs, including the gut, spleen, lung, brain, and adipose tissue (Zhang et al). The dysfunctional gut-liver axis leads to a "leaky gut", which relates to bacteria's toxic metabolites infiltrating into the circulation and the liver, leading to macrophage and neutrophil accumulation and subsequent liver fibrosis progression (Guan et al) (22)(23)(24). Recently, an increasing number of studies have shown that the intestinal flora is involved in the pathogenesis of NAFLD by affecting metabolism, intestinal endotoxin, and intestinal mucosal permeability (Liu et al).…”

Understanding endometriosis from an immunomicroenvironmental perspective

“…Impairment or imbalance of microbiota, also known as dysbiosis, is implicated in the perturbed immune responses and chronic inflammation of the hosts and, as a result, has a fundamental role in a broad spectrum of diseases. [67][68][69] As endometriosis is characterized by defective immunosurveillance and perpetuating inflammation, it is speculated that there is an inextricable link between microbiota and endometriosis. Indeed, microbiota alterations in the endometrium, cervix, vagina, and gut were detected in individuals with endometriosis compared to those without this disease, which were manifested with decreased probiotics and elevated opportunistic bacteria.…”