Dynamics of the gut-liver axis in rats with varying fibrosis severity

• Published in: International journal of biological sciences Vol. 18; no. 8; pp. 3390 - 3404
• Main Authors: Xiang, Hongyan, Liu, Zongyi, Xiang, Huanyu, Xiang, Dejuan, Xiao, Shuang, Xiao, Jing, Shen, Wei, Hu, Peng, Ren, Hong, Peng, Mingli
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher 2022
• Subjects: Animals; Bile Acids and Salts; Chromatography, Liquid; Liver Cirrhosis - metabolism; Rats; Research Paper; Tandem Mass Spectrometry; liver fibrosis; gut barrier; bile acid; gut-liver axis; gut microbiota
• ISSN: 1449-2288; 1449-2288
• DOI: 10.7150/ijbs.69833

The classic carbon tetrachloride (CCl )-induced liver injury model is widely used to study the pathogenesis of fibrosis and evaluate anti-fibrosis drugs. Here, we investigated the dynamic changes in the gut microbiota, bile acids (BAs) and the gut barrier over different fibrosis severities in a CCl -based model. 16S rDNA sequencing demonstrated that the beneficial taxon Lactobacillus was always underrepresented, and pathogens including , , , and were significantly overrepresented across liver fibrosis severities. Gut dysbiosis was more severe at the early stage of liver injury and advanced stage of fibrosis. An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis revealed that with the progress of fibrosis, unconjugated BAs in faeces were significantly decreased and conjugated BAs in serum were significantly increased. The FXR-SHP signalling pathway in the liver and ileum was statistically repressed in the fibrosis groups. Determination of lipopolysaccharide (LPS) and fluorescein isothiocyanate (FITC)-dextran levels in plasma showed that the intestinal barrier remained relatively intact in the advanced fibrosis stage. The advances in knowledge of the gut-liver axis provided by this study yield new insights for application in research and drug evaluation.