Department of Pathophysiology, Harbin Medical University, Harbin 150086, China.
Department of General Surgery, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.
Int J Biol Macromol. 2024 Feb;258(Pt 2):129052. doi: 10.1016/j.ijbiomac.2023.129052. Epub 2023 Dec 29.
Gut microbial dysbiosis has always served as a potential factor in the occurrence and development of liver fibrosis. Liver and gut microflora can regulate each other through the gut-liver axis. In this study, the 16S rRNA and RNA-seq were chosen to sequence gut microbiota alteration and liver differentially expressed genes (DEGs) in carbon tetrachloride (CCl4) included-liver fibrosis mice, and analyze the correlations between gut microbiota constituents and DEGs. Results indicated that, CCl4 significantly increased the abundance of Desulfobactera in the phylum level, destroyed gut microbiota balance in the genus levels, especially Enterorhabdus and Desulfovibrio. Through analysis, 1416 genes were found differentially expressed in mice liver tissue in the CCl4 Group, compared with the Control Group; and the DEGs were mainly involved in the lipid metabolic process and immune system process. The correlation analysis revealed that the relative abundance of microbiota phylum (Desulfobactera) and genus (Enterorhabdus and Desulfovibrio) was negatively correlated with the metabolism related genes, while positively correlated with immune-related genes and the genes enriched in PI3K-Akt signaling pathway. To sum up, CCl4 can partially regulate gene expression in metabolism, immune response and the PI3K/Akt pathway, and further maintain the stability of the gut environment in liver fibrosis mice.
肠道微生物失调一直是肝纤维化发生和发展的潜在因素。肝脏和肠道微生物群可以通过肠-肝轴相互调节。在这项研究中,选择 16S rRNA 和 RNA-seq 来测序四氯化碳(CCl4)诱导的肝纤维化小鼠肠道微生物群改变和肝脏差异表达基因(DEGs),并分析肠道微生物群组成与 DEGs 之间的相关性。结果表明,CCl4 显著增加了厚壁菌门中脱硫杆菌的丰度,破坏了属水平的肠道微生物群平衡,特别是肠杆菌属和脱硫弧菌属。通过分析,与对照组相比,CCl4 组小鼠肝脏组织中有 1416 个基因表达发生差异;差异表达基因主要参与脂质代谢过程和免疫系统过程。相关性分析表明,微生物群门(脱硫杆菌)和属(肠杆菌和脱硫弧菌)的相对丰度与代谢相关基因呈负相关,而与免疫相关基因和富含 PI3K-Akt 信号通路的基因呈正相关。综上所述,CCl4 可以部分调节代谢、免疫反应和 PI3K/Akt 通路中的基因表达,从而进一步维持肝纤维化小鼠肠道环境的稳定性。