Modulation of the gut microbiota impacts nonalcoholic fatty liver disease: a potential role for bile acids
Modulation of the gut microbiota impacts nonalcoholic fatty liver disease: a potential role for bile acids
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DOI：
10.1194/jlr.m075713
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发表时间：
2017-07-01
影响因子：
6.5
通讯作者：
Kersten, Sander
中科院分区：
文献类型：
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作者：
Janssen, Aafke W. F.;Houben, Tom;Kersten, Sander
非酒精性脂肪性肝病（NAFLD）是世界范围内最常见的肝脏疾病，但其发病机制尚不完全清楚。在这里，我们研究了肠道细菌在NAFLD中的作用，通过给小鼠喂食可发酵膳食纤维瓜尔胶（GG）来刺激肠道细菌，并通过长期口服抗生素来抑制肠道细菌。GG喂养深刻地改变了肠道微生物群组成，同时减少了饮食引起的肥胖和改善了葡萄糖耐量。引人注目的是，尽管减少了脂肪组织肿块和炎症，GG却增强了肝脏炎症和纤维化，同时血浆和肝脏胆汁酸水平显著升高。与胆汁酸升高在肝脏表型中的作用一致，用牛磺胆酸治疗小鼠刺激肝脏炎症和纤维化。与GG相比，长期口服抗生素可有效抑制肠道细菌，降低门静脉次级胆汁酸水平，减轻肝脏炎症和纤维化。GG和抗生素均不影响血浆脂多糖水平。总之，我们的数据表明，在NAFLD小鼠模型中，肠道微生物群的变化与肝脏炎症和纤维化之间存在因果关系，可能是通过胆汁酸的改变。-Janssen, a.w.f., t.h Houben， S. Katiraei， W. Dijk， L. Boutens， N. van der Bolt， Z. Wang， J. M. Brown， S. L. Hazen， S. manard， R. Shiri-Sverdlov， F. Kuipers， K. Willems van Dijk， J. Vervoort， R. Stienstra， G. J. E. J. Hooiveld， S. Kersten。肠道菌群的调节影响非酒精性脂肪性肝病：胆汁酸的潜在作用
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, yet the pathogenesis of NAFLD is only partially understood. Here, we investigated the role of the gut bacteria in NAFLD by stimulating the gut bacteria via feeding mice the fermentable dietary fiber, guar gum (GG), and suppressing the gut bacteria via chronic oral administration of antibiotics. GG feeding profoundly altered the gut microbiota composition, in parallel with reduced diet-induced obesity and improved glucose tolerance. Strikingly, despite reducing adipose tissue mass and inflammation, GG enhanced hepatic inflammation and fibrosis, concurrent with markedly elevated plasma and hepatic bile acid levels. Consistent with a role of elevated bile acids in the liver phenotype, treatment of mice with taurocholic acid stimulated hepatic inflammation and fibrosis. In contrast to GG, chronic oral administration of antibiotics effectively suppressed the gut bacteria, decreased portal secondary bile acid levels, and attenuated hepatic inflammation and fibrosis. Neither GG nor antibiotics influenced plasma lipopolysaccharide levels. In conclusion, our data indicate a causal link between changes in gut microbiota and hepatic inflammation and fibrosis in a mouse model of NAFLD, possibly via alterations in bile acids.-Janssen, A. W. F., T. Houben, S. Katiraei, W. Dijk, L. Boutens, N. van der Bolt, Z. Wang, J. M. Brown, S. L. Hazen, S. Mandard, R. Shiri-Sverdlov, F. Kuipers, K. Willems van Dijk, J. Vervoort, R. Stienstra, G. J. E. J. Hooiveld, and S. Kersten. Modulation of the gut microbiota impacts nonalcoholic fatty liver disease: a potential role for bile acids.