Department of Internal Medicine III, University Hospital RWTH Aachen, 52074 Aachen, Germany.
Department of Pathology, Klinikum Braunschweig, 38118 Braunschweig, Germany.
Int J Mol Sci. 2019 Jan 14;20(2):308. doi: 10.3390/ijms20020308.
Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in western countries, with a continuously rising incidence. Gut-liver communication and microbiota composition have been identified as critical drivers of the NAFLD progression. Hence, it has been shown that microbiota depletion can ameliorate high-fat diet or western-diet induced experimental Non-alcoholic steatohepatitis (NASH). However, its functional implications in the methionine-choline dietary model, remain incompletely understood. Here, we investigated the physiological relevance of gut microbiota in methionine-choline deficient (MCD) diet induced NASH. Experimental liver disease was induced by 8 weeks of MCD feeding in wild-type (WT) mice, either with or without commensal microbiota depletion, by continuous broad-spectrum antibiotic (AB) treatment. MCD diet induced steatohepatitis was accompanied by a reduced gut microbiota diversity, indicating intestinal dysbiosis. MCD treatment prompted macroscopic shortening of the intestine, as well as intestinal villi in histology. However, gut microbiota composition of MCD-treated mice, neither resembled human NASH, nor did it augment the intestinal barrier integrity or intestinal inflammation. In the MCD model, AB treatment resulted in increased steatohepatitis activity, compared to microbiota proficient control mice. This phenotype was driven by pronounced neutrophil infiltration, while AB treatment only slightly increased monocyte-derived macrophages (MoMF) abundance. Our data demonstrated the differential role of gut microbiota, during steatohepatitis development. In the context of MCD induced steatohepatitis, commensal microbiota was found to be hepatoprotective.
非酒精性脂肪性肝病（NAFLD）是西方国家最常见的肝脏疾病，其发病率持续上升。肠道-肝脏通讯和微生物群落组成已被确定为 NAFLD 进展的关键驱动因素。因此，已经表明微生物群落耗竭可以改善高脂肪饮食或西方饮食诱导的实验性非酒精性脂肪性肝炎（NASH）。然而，其在蛋氨酸-胆碱饮食模型中的功能意义仍不完全清楚。在这里，我们研究了肠道微生物群在蛋氨酸-胆碱缺乏（MCD）饮食诱导的 NASH 中的生理相关性。通过连续广谱抗生素（AB）处理，在野生型（WT）小鼠中用 8 周的 MCD 喂养诱导实验性肝病，要么存在共生微生物群落耗竭，要么不存在。MCD 饮食诱导的肝炎伴随着肠道微生物多样性的降低，表明肠道菌群失调。MCD 处理促使肠道宏观缩短，组织学上的肠绒毛也变短。然而，MCD 处理小鼠的肠道微生物群落组成既不像人类 NASH，也不会增加肠道屏障完整性或肠道炎症。在 MCD 模型中，与具有共生微生物群落的对照小鼠相比，AB 处理导致肝脂肪变性活性增加。这种表型是由明显的中性粒细胞浸润驱动的，而 AB 处理仅略微增加单核细胞衍生的巨噬细胞（MoMF）的丰度。我们的数据表明，肠道微生物群在肝脂肪变性发展过程中发挥了不同的作用。在 MCD 诱导的肝脂肪变性中，共生微生物群被发现具有肝脏保护作用。
