Potential mechanisms of traditional Chinese medicine in the treatment of liver cirrhosis: a focus on gut microbiota

Abstract

Cirrhosis, a pathological stage that develops from various chronic liver diseases, is characterized by liver fibrosis, pseudolobular formation, and chronic inflammation. When it progresses to the decompensated phase, the mortality rate of cirrhosis can reach 80%. The role of gut microbiota in the progression of liver diseases has received significant attention. Numerous studies have shown that regulating gut microbiota has significant therapeutic effects on preventing and reversing liver cirrhosis. This article reviewed the mechanisms by which gut microbiota influence liver cirrhosis, explaining the effective therapeutic effects of traditional Chinese medicine. Through multi-directional regulation involving signaling pathways, gut microbiota diversity, and restoration of intestinal barrier function, traditional Chinese medicine has been promising in ameliorating liver cirrhosis, providing treatment options and pharmacological guidance for the occurrence and development of liver cirrhosis.

Keywords: gut microbiota; liver cirrhosis; microbial metabolites; natural products; traditional Chinese medicine.

Figure 1

Links among liver cirrhosis, gut microbiota, and TCM. The figure is drawn with Figdraw.com.

Figure 2

Pathogenesis of cirrhosis based on the enterohepatic circulation. The figure is drawn with Figdraw.com. The figure is divided into three sections from top to bottom: (A) Intestinal barrier: The effect of intestinal microbes, metabolites such as BAs and endotoxin on intestinal mucosal barrier function, including increased permeability and bacterial translocation. (B) Portal vein: Factors delivered to the liver via the portal vein, such as cytokines and microbiota-associated molecular patterns (MAMPs), which induce the activation of immune cells such as Kupffer cells, leading to inflammation and endotoxemia. (C) Liver microenvironment: After microbial-derived metabolites reach the liver through the portal vein, they trigger a series of reactions in the liver, including the activation of macrophages and HSCs, and may lead to liver fibrosis/cirrhosis, portal hypertension, and eventually liver failure.

Figure 3

Comparison of intact and impaired intestinal barriers. The figure is drawn with Figdraw.com. (A) In the intact intestinal barrier, the intestinal microbial diversity is normal, the mucus layer limits the colonization and transfer of bacteria, the beneficial bacteria repel the invasion of pathogenic bacteria, and the complex structure of TJ together to maintain the selective permeability of intestinal epithelial cells, allowing nutrients and water ingested by the host to pass through and preventing harmful microorganisms and their metabolites from entering the portal vein through the intestinal barrier. Immune cells secrete various cytokines to timely remove invading pathogens and toxins and strengthen the intestinal barrier. (B) After the intestinal barrier is damaged, the mucus layer becomes loose and thick. Harmful microorganisms and their metabolites break through the mucus layer, destroy the intestinal tight-junction apparatus, and compete with beneficial bacteria and intestinal epithelial cells for nutrients, leading to increased intestinal permeability. Bacteria, toxins and other harmful molecules stimulate the intestinal immune barrier system, leading to enhanced immune activity and reduced microbial diversity. Finally, it further increases BT and intestinal leakage.

Figure 4

Specific mechanisms by which microbial metabolites act on cirrhosis. The figure is drawn with Figdraw.com.