Metformin alleviates liver fibrosis in mice by enriching Lactobacillus sp. MF-1 in the gut microbiota.
Metformin alleviates liver fibrosis in mice by enriching Lactobacillus sp. MF-1 in the gut microbiota.
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DOI：
10.1016/j.bbadis.2023.166664
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发表时间：
2023-03
期刊：
影响因子：
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通讯作者：
Tao Yang;Qijie Guan;Jin-song Shi;Zhenghong Xu;Yan Geng
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文献类型：
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作者：
Tao Yang;Qijie Guan;Jin-song Shi;Zhenghong Xu;Yan Geng
背景肝纤维化与肠道生态失调有关。二甲双胍给药已成为治疗器官纤维化的有前景的方法。本研究旨在探讨二甲双胍是否通过增强四氯化碳（CCl 4）诱导的肝纤维化小鼠肠道菌群来改善肝纤维化及其机制。我们给予抗生素治疗，并进行粪便微生物群移植（FMT）和基于16 S rRNA的微生物组分析，以评估肠道微生物组对二甲双胍治疗的肝纤维化的影响。我们分离出的细菌菌株，优选富集二甲双胍和评估其抗纤维化effics. ResultsMetaldehyde治疗修复的四氯化碳处理的小鼠的肠道完整性。它减少了结肠组织中的细菌数量，降低了门静脉脂多糖（LPS）水平。二甲双胍处理的CCl 4小鼠的FMT减轻了它们的肝纤维化，降低了它们的门静脉LPS水平。从粪便中筛选出显著改变的肠道微生物群，并命名为乳杆菌属MF-1（Lactobacillus sp. MF-1）。在CCl 4处理的小鼠中，每天灌胃L.sp. MF-1可维持肠道完整性，抑制细菌移位，并减少肝纤维化。机制上，二甲双胍或L.sp. MF-1可抑制肠上皮细胞凋亡，恢复回肠中的CD 3+肠上皮内淋巴细胞和结肠中的CD 4 + Foxp 3+固有层淋巴细胞。结论二甲双胍及其富集物L. sp. MF-1可通过恢复免疫功能，增强肠屏障，减轻肝纤维化。
BackgroundLiver fibrosis is associated with gut dysbiosis. Metformin administration has emerged as a promising method for the treatment of organ fibrosis. We aimed to investigate whether metformin ameliorates liver fibrosis by enhancing the gut microbiota in mice with carbon tetrachloride (CCl4)-induced liver fibrosis and the underlying mechanism.Materials and methodsA liver fibrosis mouse model was established, and the therapeutic effects of metformin were observed. We administered antibiotic treatment and performed fecal microbiota transplantation (FMT), and 16S rRNA-based microbiome analysis to evaluate the effects of the gut microbiome on metformin-treated liver fibrosis. We isolated the bacterial strain preferably enriched by metformin and assessed its antifibrotic effects.ResultsMetformin treatment repaired the gut integrity of the CCl4-treated mice. It reduced the number of bacteria in colon tissues and reduced the portal vein lipopolysaccharide (LPS) levels. The FMT performed on the metformin-treated CCl4mice alleviated their liver fibrosis and reduced their portal vein LPS levels. The markedly changed gut microbiota was screened out from the feces and named Lactobacillus sp. MF-1 (L.sp. MF-1). In the CCl4-treated mice, daily gavage ofL.sp. MF-1 maintained gut integrity, inhibited bacterial translocation, and reduced liver fibrosis. Mechanistically, metformin orL.sp. MF-1 inhibited the apoptosis of intestinal epithelial cells and restored CD3+intestinal intraepithelial lymphocytes in the ileum and CD4+Foxp3+lamina propria lymphocytes in the colon.ConclusionsMetformin and its enrichedL.sp. MF-1 can reinforce the intestinal barrier to alleviate liver fibrosis by restoring immune function.