The Role of Gut Microbiota in Some Liver Diseases: From an Immunological Perspective

Abstract

Gut microbiota is a microecosystem composed of various microorganisms. It plays an important role in human metabolism, and its metabolites affect different tissues and organs. Intestinal flora maintains the intestinal mucosal barrier and interacts with the immune system. The liver is closely linked to the intestine by the gut-liver axis. As the first organ that comes into contact with blood from the intestine, the liver will be deeply influenced by the gut microbiota and its metabolites, and the intestinal leakage and the imbalance of the flora are the trigger of the pathological reaction of the liver. In this paper, we discuss the role of gut microbiota and its metabolites in the pathogenesis and development of autoimmune liver diseases((including autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis), metabolic liver disease such as non-alcoholic fatty liver disease, cirrhosisits and its complications, and liver cancer from the perspective of immune mechanism. And the recent progress in the treatment of these diseases was reviewed from the perspective of gut microbiota.

Keywords: gut microbiota; immunity; liver diseases; metabolism; review.

Figure 1

The mechanical barrier is mainly composed of mucus, IECs and TJs between cells, which can maintain normal permeability of intestine, and prevent intestinal bacteria, antigens and other substances from entering the lamina propria. After ingesting, processing and presenting exogenous antigens, the immune response is coordinated by secreting cytokines and producing antibodies, further activating T and B lymphocytes to establish an effective adaptive immune response and inducing mucosal immune response or immune tolerance. Once bound to luminal antigens, DC pattern recognition receptors express co-stimulatory molecules and cytokines involved in regulating the differentiation of Th cells and Treg cells into CD4+ T cells, maintaining Treg/Th17 balance and forming immune homeostasis. The gut microbiota promotes the differentiation of IgA-secreting plasma cells by activating DC cells to secret B cell activating factor, thereby releasing sIgA to encapsulate bacteria to form a complex.

Figure 2

After the activation of the adaptive immune system, some bacterial products, such as LPS, or inflammatory cytokines and chemokines produced, flow into the portal vein system through the upper and lower mesenteric veins, and finally into the liver, causing the activation of kupffer cells and hepatic stellate cells(HSCs), thus further causing the occurrence of liver inflammation and fibrosis. Metabolic products of gut microbiota cause inflammation in liver tissue and affect liver metabolism, thus promoting the occurrence of various liver diseases, and eventually develop into cirrhosis and even liver cancer.