Role of Intestinal Microbes in Chronic Liver Diseases

Abstract

With the recent availability and upgrading of many emerging intestinal microbes sequencing technologies, our research on intestinal microbes is changing rapidly. A variety of investigations have found that intestinal microbes are essential for immune system regulation and energy metabolism homeostasis, which impacts many critical organs. The liver is the first organ to be traversed by the intestinal portal vein, and there is a strong bidirectional link between the liver and intestine. Many intestinal factors, such as intestinal microbes, bacterial composition, and intestinal bacterial metabolites, are deeply involved in liver homeostasis. Intestinal microbial dysbiosis and increased intestinal permeability are associated with the pathogenesis of many chronic liver diseases, such as alcoholic fatty liver disease (AFLD), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), chronic hepatitis B (CHB), chronic hepatitis C (CHC), autoimmune liver disease (AIH) and the development of hepatocellular carcinoma (HCC). Intestinal permeability and dysbacteriosis often lead to Lipopolysaccharide (LPS) and metabolites entering in serum. Then, Toll-like receptors activation in the liver induces the exposure of the intestine and liver to many small molecules with pro-inflammatory properties. And all of these eventually result in various liver diseases. In this paper, we have discussed the current evidence on the role of various intestinal microbes in different chronic liver diseases. As well as potential new therapeutic approaches are proposed in this review, such as antibiotics, probiotics, and prebiotics, which may have an improvement in liver diseases.

Identification of the Microbiome Associated with Prognosis in Patients with Chronic Liver Disease

“…The intestinal barrier and liver physiology underscore a bidirectional relationship in which both organ systems significantly influence each other’s functional and health status. This relationship has been increasingly recognized for its critical role in the pathogenesis and progression of various liver diseases, including non-alcoholic fatty liver disease, alcoholic liver disease, hepatitis, and cirrhosis [ 18 , 19 ]. The composition of the gut microbiome and its metabolic products can profoundly affect liver health through multiple mechanisms, including the modulation of immune responses, the production of toxic metabolites, and their impact on metabolic homeostasis.…”

Small Intestinal Bacterial Overgrowth and Non-Alcoholic Fatty Liver Disease: What Do We Know in 2023?

“…The gut microbiota may be involved in the pathogenesis of NAFLD, via several factors [ 87 ]: Body weight—an increase in body weight contributes to a decrease in the diversity of the gut microbiota [ 92 ]; Anatomical and functional changes in the intestinal barrier (defined as the immune barrier, the intestinal vascular barrier, and the hepatic barrier). Intestinal dysbiosis, intensifying the translocation of bacteria through the portal vein to the liver (endotoxemia), enhances inflammatory responses in the liver [ 93 ], Specific patterns pro-inflammatory compounds of the intestinal microbiome—PAMPs and MAMPs such as LPS, peptidoglycans and lipopeptides, microbial DNA, circulating proinflammatory cytokines (IL-1, IL-6, INF-γ, and TNF-α) may contribute to the inflammatory response and fibrosis in patients with NAFLD [ 87 , 94 ]; Could influence the metabolic and inflammatory state of the liver through the release of anti-inflammatory compounds (short chain fatty acids-SCFA) that bind to G protein-coupled receptors (GPCRs) induce hepatic lipids and glucose homeostasis, the regulation of intestinal integrity and intrinsic immune defenses [ 95 ]. …”

“…Could influence the metabolic and inflammatory state of the liver through the release of anti-inflammatory compounds (short chain fatty acids-SCFA) that bind to G protein-coupled receptors (GPCRs) induce hepatic lipids and glucose homeostasis, the regulation of intestinal integrity and intrinsic immune defenses [ 95 ].…”

Investigating causal associations among gut microbiota, metabolites, and liver diseases: a Mendelian randomization study

“…Recently, there has been growing evidence that intestinal flora is closely related to human health and is involved in the etiology of various complex diseases, including liver diseases ( 9 , 10 ). However, there is controversy among these studies.…”