Intestinal Microbiota and Liver Diseases: Insights into Therapeutic Use of Traditional Chinese Medicine

Abstract

Liver disease is a leading cause of global morbidity and mortality, for which inflammation, alcohol use, lipid metabolic disorders, disturbance to bile acid metabolism, and endotoxins are common risk factors. Traditional Chinese Medicine (TCM) with its "holistic approach" is widely used throughout the world as a complementary, alternative therapy, due to its clinical efficacy and reduced side effects compared with conventional medicines. However, due to a lack of reliable scientific evidence, the role of TCM in the prevention and treatment of liver disease remains unclear. Over recent years, with the rapid development of high-throughput sequencing, 16S rRNA detection, and bioinformatics methodology, it has been gradually recognized that the regulation of intestinal microbiota by TCM can play a substantial role in the treatment of liver disease. To better understand how TCM regulates the intestinal microbiota and suppresses liver disease, we have reviewed and analyzed the results of existing studies and summarized the relationship and risk factors between intestinal microbiota and liver disease. The present review summarizes the related mechanisms by which TCM affects the composition and metabolites of the intestinal microbiome.

Figure 1

The link between gut microbiota and liver disease risk factors.Inflammation, EnEth, lipid metabolism, bile acid metabolism, and endotoxin levels are the common risk factors for liver diseases induced by intestinal microbiotas and their metabolites. (a) Inflammation: it is one of the most typical features of liver disease and occurs at all stages of disease development. (b) Bile acid metabolism: bile acid is an important part of bile, and intestinal floras regulate its metabolism through the FXR/TGR5 pathway. (c) Ethanol: in addition to exogenous alcohol intake, intestinal flora also can produce a large amount of ethanol (EnEth), affecting intestinal barrier and BT. (d) Lipid metabolism: gut microbiota influence on lipid metabolism may be mediated through metabolites and LPS. NAFLD, nonalcoholic fatty liver disease; HCC, hepatocellular carcinoma; LPS, lipopolysaccharides; PAMPs, pathogen-associated molecular patterns; BT, bacteria translocation; FXR, farnesoid X receptor; EnEth, endogenous ethanol; ROS, oxidative stress, and reactive oxygen species; SCFAs, short-chain fatty acids; TG, triglycerides; FFA, free fatty acids.

Figure 2

TCM affects liver disease progression by regulating intestinal microbiotas. The composition of intestinal microbiotas and their metabolites can be regulated by TCM. For example, Chinese herbs can increase SCFA levels by promoting abundance of Clostridium and Firmicutes, elevate bile acid levels by increasing Lactobacillus and Bifidobacterium abundance, and reduce levels of LPS and inflammatory factors by decreasing populations of Klebsiella and Haemophilus. The specific mechanisms include reducing inflammatory injury and oxidative stress, regulating body immunity, improving lipid metabolism, protecting intestinal barrier, and reversing hepatic fibrosis. TCM, traditional Chinese medicine; LPS, lipopolysaccharides; BT, bacterial translocation; EnEth, endogenous ethanol; SCFAs, short-chain fatty acids; FFA, free fatty acids.