Gut microbiome, liver immunology, and liver diseases

Abstract

The gut microbiota is a complex and plastic consortium of microorganisms that are intricately connected with human physiology. The liver is a central immunological organ that is particularly enriched in innate immune cells and constantly exposed to circulating nutrients and endotoxins derived from the gut microbiota. The delicate interaction between the gut and liver prevents accidental immune activation against otherwise harmless antigens. Work on the interplay between the gut microbiota and liver has assisted in understanding the pathophysiology of various liver diseases. Of immense importance is the step from high-throughput sequencing (correlation) to mechanistic studies (causality) and therapeutic intervention. Here, we review the gut microbiota, liver immunology, and the interaction between the gut and liver. In addition, the impairment in the gut-liver axis found in various liver diseases is reviewed here, with an emphasis on alcohol-associated liver disease (ALD), nonalcoholic fatty liver disease (NAFLD), and autoimmune liver disease (AILD). On the basis of growing evidence from these preclinical studies, we propose that the gut-liver axis paves the way for targeted therapeutic modalities for liver diseases.

Keywords: Alcohol liver disease; Autoimmune liver disease; Gut–liver axis; Microbiome; Nonalcoholic fatty liver disease.

Fig. 1

Interplay between the liver and gut microbiota in chronic liver diseases. Intestinal dysbiosis is the cornerstone of the impaired gut–liver axis, with different altered profiles in ALD, NAFLD, and AILD. Significant changes include (1) increased microbial invasion and impaired intestinal barrier and (2) activation of immune signaling and accumulation of toxins (especially in ALD and NAFLD) found in the liver. Changes in the gut and liver are connected by the portal vein, systemic circulation and bile acid metabolism. Finally, chronic inflammation and recurrent proliferation within the liver lead to cirrhosis. HFD high-fat diet, PAMP pathogen-associated molecular pattern, BA bile acid, AMP antimicrobial peptide, DC dendritic cell, TMA trimethylamine, TLR Toll-like receptor, DAMP damage-associated molecular pattern, HSC hepatic stellate cell