Gut microbiota and liver diseases

In traditional impressions, there is no obvious connection between the intestines and the liver, but in fact, both are related in structure and function. Blood from the intestines flows back to the liver through the portal vein, which accounts for most of the liver's blood supply. If the intestinal microbiota is imbalanced, bacterial products and gut-derived toxins reach the liver via the portal vein, activating pro-inflammatory responses and triggering various diseases. Therefore, the intestinal microbiota provides new ideas for the treatment of liver diseases.

Non-alcoholic fatty liver disease (NAFLD)

Non-alcoholic fatty liver disease (NAFLD) is a complex metabolic disease, some of which may progress to non-alcoholic steatohepatitis (NASH), and then worsen to liver fibrosis and cirrhosis, even liver cancer. It was previously believed that NAFLD was caused by obesity and genetic factors, but recent studies have found that the number of thick-walled bacteria in NAFLD patients increases, while the number of Bacteroidetes decreases, indicating a clear relationship between NAFLD and intestinal flora. Small intestinal bacterial overgrowth produces ethanol and other volatile compounds, and ethanol can promote the accumulation of reactive oxygen species, leading to liver damage. Meanwhile, persistent low-density volatile compounds reach the liver through the intestinal mucosa and portal vein, causing liver damage similar to that of ethanol. Experiments comparing different probiotics (Lactobacillus casei, Lactobacillus rhamnosus, Bifidobacterium) on a high-fat diet-induced metabolic syndrome mouse model showed that the three probiotics reduced the degree of inflammatory response in mice to varying extents, indicating that different probiotics may protect the liver and inhibit the occurrence of NAFLD through different pathways.

Alcoholic liver disease (ALD)

Long-term excessive alcohol consumption increases the permeability of the intestinal epithelial barrier. In vitro experiments have shown that ethanol and its toxic metabolite acetaldehyde damage the intestinal epithelial barrier by disrupting the tight junction structure of Caco-2 intestinal epithelial cells. At the same time, a long-term alcohol environment in the intestines reduces intestinal motility, leading to bacterial overgrowth, an imbalance in the intestinal microbiota, and elevated levels of serum endotoxins. Endotoxins can reach the liver through the increased permeability of the intestinal epithelial barrier or via the bloodstream through the portal vein. A principal component analysis of the intestinal microbiota genomes of alcoholics and healthy individuals revealed significant differences between the two groups. The study also found that the levels of antimicrobial proteins Re93b and Re939 were reduced in alcoholics. Another study using length heterogeneity PCR fingerprinting and multiplex fragment pyrosequencing analyzed the intestinal microbiota composition of alcoholics and healthy individuals, confirming that alcoholics had lower abundances of Bacteroidetes and higher abundances of Proteobacteria, with changes in the microbiota accompanied by elevated levels of endotoxins in the blood.

Cirrhosis

Cirrhosis can be seen as the end stage of chronic liver disease, characterized by liver fibrosis, disordered liver parenchyma structure, and nodular regeneration of liver cells, which can lead to liver failure in the later stages. Patients with cirrhosis have reduced bile secretion and portal hypertension, which can affect the growth and structure of the intestinal microbiota, causing small intestinal bacterial overgrowth and increased intestinal permeability, leading to the translocation of intestinal bacteria and their products, inducing liver inflammation and fibrosis. In pre-treated rat models of cirrhosis, the incidence of intestinal microbiota translocation increased, and the expression of corresponding pro-inflammatory factors TNF-α and IL-6 in serum increased, while the expression of G protein-coupled receptor-4 (GPR-4) decreased. GPR-4 is mainly involved in recruiting polymorphonuclear leukocytes to prevent microbiota translocation. Qin et al. used metagenomic methods to analyze the intestinal microbiota of cirrhosis patients, finding that the abundance of Bacteroidetes and Firmicutes decreased, while Streptococcus and Veillonella increased, both of which are oral bacteria. The increase of Streptococcus and Veillonella indicates the invasion of oral bacteria into the intestines, which may be related to the reduced secretion of bile and gastric acid during cirrhosis, thereby lowering the defense against exogenous bacteria. Under normal circumstances, bile acids and gastric acid have antibacterial functions and can maintain the integrity of the gastrointestinal barrier, preventing oral bacteria from colonizing the lower digestive tract. In summary, cirrhosis patients have an increase in potential pathogenic bacteria in the intestines and a decrease in beneficial bacteria, and the translocation of intestinal microbiota and their derivatives can cause systemic and liver inflammation and fibrosis.inflammation and liver fibrosis.

Autoimmune hepatitis (AIH)

Autoimmune hepatitis (AIH) is a rare idiopathic syndrome of immune damage to liver cells, usually associated with autoantibodies, but the intestinal microbiota has also been confirmed to play an important role in the occurrence, development, and treatment of autoimmune liver diseases. Lin et al. found that compared to healthy volunteers, AIH patients had reduced structural proteins in intestinal epithelial cells and a decrease in anaerobic bacteria (such as Bifidobacterium and Lactobacillus), reflecting increased intestinal permeability, dysbiosis, and bacterial translocation in AIH patients. Additionally, damage to the intestinal barrier may be an important cause of AIH. Muhammed et al. established a novel AIH model using transgenic mice and found a significant connection between the intestinal microbiota and AIH, which affects the progression of AIH.

Summary

In summary, the intestinal microbiota can affect liver health through the production of bacterial products, changes in intestinal permeability, and other pathways, and these factors may interact and influence each other in multiple ways.

Note: This article is for informational purposes only and should not be considered medical guidance.