Changes in the composition of intestinal microbiota in mice with acute liver failure induced by D-galactosamine

Abstract

Objective: To investigate the changes in the composition of intestinal microbiota in mice with acute liver failure and identify characteristic bacteria, and to provide a basis for the diagnosis and treatment of acute liver failure with intestinal microbiota disorders. Methods: A total of 30 specific pathogen-free male BALB/c mice were used in this study, including 25 mice in the model group and 5 mice in the control group. An acute liver failure model was induced by D-galactosamine. Microbial DNA was extracted from intestinal contents in different segments of the lower digestive tract (ileum and colon) and feces and then were amplified using PCR. The regions of 16S V3-V4 were subjected to high-throughput sequencing, followed by bioinformatics analyses, including OTU hierarchical clustering, species annotation, alpha-diversity analysis, and LEfSe (LDA Effect Size) analysis. Comparison of continuous data was made using t-test, while comparison of categorical data was made using χ2 test. Results: A total of 10 mice survived in the two groups, with 80% mortality rate in the model group. The alpha-diversity analysis revealed increased bacterial diversity and abundance in the ileum, increased bacterial diversity and reduced bacterial abundance in the colon, and reduced bacterial diversity and insignificantly changed bacterial abundance in feces in the model group compared with the control group. Based on the optimized classification level, significantly reduced abundance of Clostridiaceae (44.95% ± 19.28% vs 7.51% ± 16.57%, P = 0.011) in the ileum, whereas significantly increased abundance of Rikenellaceae (1.08% ± 1.01% vs 4.18% ± 2.39%, P = 0.028), S24-7 (4.75% ± 4.87% vs 22.77% ± 13.05%, P = 0.020), and F16 (0.24% ± 0.28% vs 2.18% ± 1.61%, P = 0.029) in the colon were found in model group compared with the control group. The LEfSe analysis demonstrated that there were significant differences in Staphylococcaceae and S24-7 between the two groups, and S24-7 could be defined as the characteristic bacteria. Conclusion: Intestinal microbiota disorders, especially the excessive growth of microbes in the ileum, are observed in mice with acute liver failure. Moreover, acute liver failure may be closely associated with the excessive growth of S24-7.