Abstract
The important role of human gut microbiota in liver diseases has long been recognized as dysbiosis and the translocation of certain microbes from the gut to liver. With the development of high-throughput DNA sequencing, the complexity and integrity of the gut microbiome in the whole spectrum of liver diseases is emerging. Specific patterns of gut microbiota have been identified in liver diseases with different causes, including alcoholic, non-alcoholic, and virus induced liver diseases, or even at different stages, ranging from steatohepatitis, fibrosis, cirrhosis, to hepatocellular carcinoma. At the same time, the mechanism of how microbiota contributes to liver diseases goes beyond the traditional function of the gut–liver axis which could lead to liver injury and inflammation. With the application of proteomics, metabolomics, and modern molecular technologies, more microbial metabolites and the complicated interaction of microbiota with host immunity come into our understanding in the liver pathogenesis. Germ-free animal models serve as a workhorse to test the function of microbiota and their derivatives in liver disease models. Here, we review the current evidence on the relationship between gut microbiota and liver diseases, and the mechanisms underlying this phenotype. In addition to original liver diseases, gut microbiota might also affect liver injury in systemic disorders involving multiple organs, as in the case of COVID-19 at a severe state. A better understanding of the gut microbial contribution to liver diseases might help us better benefit from this guest–host relationship and pave the way for novel therapies.
Highlights
The important role of human gut microbiota in liver diseases has long been recognized as dysbiosis and the translocation of certain microbes from the gut to liver
We center on the recent advance in our perception of how gut microbiota contributes to chronic liver disease
We explore the evidence for the underlying mechanism of action of the gut microbiota on hepatic function, from two major perspectives, immune calibration and metabolic regulation
Summary
Human gut microbiota contains trillions of microbes, contributing to human health and diseases through various routes of mechanism. Human studies have demonstrated compositional alterations of microbiota in diseases versus health, including those intensively studied in inflammatory bowel disease (IBD), colon cancer, diabetes, and relatively less in liver diseases [4]. We center on the recent advance in our perception of how gut microbiota contributes to chronic liver disease. 75% of the liver’s blood supply comes from the portal vein, which consists of blood from the intestines and spleen. This special physiological construction of the liver ensures its consistent interaction with the gut-resident microorganisms and their metabolites. The alterations of gut microbiota in COVID-19 patients have been studied [13]. We explore the evidence for the underlying mechanism of action of the gut microbiota on hepatic function, from two major perspectives, immune calibration and metabolic regulation
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