Impact of Gut Microbiome on Gut Permeability in Liver and Gut Diseases

Abstract

Hepatobiliary and gastrointestinal conditions, including chronic liver diseases and inflammatory bowel disease, are associated with significant morbidity and mortality globally. While the pathophysiology and symptoms vary from one disease to another, aberrations of the gut microbiome with deleterious microbial products affecting the intestinal barrier are common in patients suffering from these diseases. In this review, we summarize changes in the gut microbiome associated with various disease states and detail their role in gut barrier disruption and in modulating disease progression. Further, we discuss therapeutic interventions and precision medicine approaches targeting the microbiome, which have shown promise in alleviating these chronic illnesses in mouse models and patients.

Keywords: ALD; CLDs; IBD; MASLD; PSC; gut microbiome.

Figure 1

Various liver and gut diseases are associated with common aberrations of the bacterial, fungal, and viral microbiomes. A summary depicting the overall significant changes in the gut bacteriome, mycobiome, and virome compositions in chronic liver and gut diseases. ↑ denotes increase, whereas ↓ denotes decrease. ALD, alcohol-associated liver disease; IBD, inflammatory bowel disease; MASLD, metabolic dysfunction-associated steatohepatitis; PSC, primary sclerosing cholangitis. Created with a license from biorender.com.

Figure 2

Common pathophysiological steps in chronic liver disease related to microbial products affecting the gut barrier. A comparative analysis between normal intestinal homeostasis in healthy individuals and the dysregulated state in patients with chronic liver diseases. In healthy individuals, an intact gut barrier prevents the translocation of microbial toxins into the bloodstream. Furthermore, the production of short-chain fatty acids (SCFAs) by commensal bacteria provides a protective, anti-inflammatory environment in the gut. In contrast, dysbiosis of the gut microbiome (increased abundance of pathobionts and decreased abundance of beneficial microbes, including SCFA producers) and a related increase in toxic microbial products lead to intestinal epithelial injury (e.g., disruption of tight junctions), chronic inflammation, and gut barrier dysfunction in patients with chronic liver diseases. This facilitates the translocation of microbial toxins [lipopolysaccharides (LPSs), ethanol, and fungal toxins] from the gut to the liver via the portal circulation, contributing to hepatic inflammation and fibrosis. ↑ denotes increase, whereas ↓ denotes decrease. Created with a license from biorender.com.