Antibiotic effects on gut microbiota modulate diet-induced metabolic dysfunction-associated steatohepatitis development in C57BL/6 mice

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Shun Takano, Koudai Kani, Kaichi Kasai, Naoya Igarashi, Miyuna Kato, Kana Goto, Yudai Matsuura, Mayuko Ichimura-Shimizu, Shiro Watanabe, Koichi Tsuneyama, Yukihiro Furusawa, Yoshinori Nagai
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Abstract

The potential involvement of the gut microbiota in metabolic dysfunction-associated steatohepatitis (MASH) pathogenesis has garnered increasing attention. In this study, we elucidated the link between high-fat/cholesterol/cholate-based (iHFC)#2 diet-induced MASH progression and gut microbiota in C57BL/6 mice using antibiotic treatments. Treatment with vancomycin (VCM), which targets gram-positive bacteria, exacerbated the progression of liver damage, steatosis, and fibrosis in iHFC#2-fed C57BL/6 mice. The expression levels of inflammation- and fibrosis-related genes in the liver significantly increased after VCM treatment for 8 weeks. F4/80+ macrophage abundance increased in the livers of VCM-treated mice. These changes were rarely observed in the iHFC#2-fed C57BL/6 mice treated with metronidazole, which targets anaerobic bacteria. A16S rRNA sequence analysis revealed a significant decrease in α-diversity in VCM-treated mice compared with that in placebo-treated mice, with Bacteroidetes and Firmicutes significantly decreased, while Proteobacteria and Verrucomicrobia increased markedly. Finally, VCM treatment dramatically altered the level and balance of bile acid (BA) composition in iHFC#2-fed C57BL/6 mice. Thus, the VCM-mediated exacerbation of MASH progression depends on the interaction between the gut microbiota, BA metabolism, and inflammatory responses in the livers of iHFC#2-fed C57BL/6 mice.

抗生素对肠道微生物群的影响可调节 C57BL/6 小鼠饮食诱导的代谢功能障碍相关性脂肪性肝炎的发展。
肠道微生物群在代谢功能障碍相关性脂肪性肝炎(MASH)发病机制中的潜在参与已引起越来越多的关注。在这项研究中,我们利用抗生素疗法阐明了高脂/胆固醇/胆酸盐基(iHFC)#2 饮食诱导的 MASH 进展与 C57BL/6 小鼠肠道微生物群之间的联系。针对革兰氏阳性菌的万古霉素(VCM)会加剧 iHFC#2 喂养的 C57BL/6 小鼠肝损伤、脂肪变性和纤维化的进展。VCM 治疗 8 周后,肝脏中炎症和纤维化相关基因的表达水平明显升高。经 VCM 处理的小鼠肝脏中 F4/80+ 巨噬细胞数量增加。用甲硝唑(针对厌氧菌)治疗 iHFC#2 饲喂的 C57BL/6 小鼠很少观察到这些变化。A16S rRNA 序列分析表明,与安慰剂处理的小鼠相比,VCM 处理的小鼠体内的 α 多样性显著下降,其中类杆菌和固缩菌显著减少,而变形菌和蛭弧菌显著增加。最后,VCM 治疗极大地改变了 iHFC#2 喂养的 C57BL/6 小鼠的胆汁酸(BA)组成水平和平衡。因此,VCM 介导的 MASH 进展加剧取决于肠道微生物群、胆汁酸代谢和 iHFC#2 喂养的 C57BL/6 小鼠肝脏中的炎症反应之间的相互作用。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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