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首页 » Nature报道 » Nature:肠道微生物群落改变可造成肥胖和脂肪肝

Nature:肠道微生物群落改变可造成肥胖和脂肪肝

来源:生物探索 2012-02-07 11:00

2月1日,网络出版Nature杂志上发表了耶鲁大学科学家的研究成果。研究者发现一类蛋白质可以改变胃里的微生物数量,从而引发肥胖和慢性肝病,而且研究还表明这具有传染性。从而扩展了早前耶鲁的研究——一类蛋白导致的相似微生物群落失调,增加肠道疾病如结肠炎的风险。

耶鲁研究人员杰出的发现是,肠道环境的改变会导致肥胖和肝脏疾病,并且这种改变在小鼠群体里具有传染性。“当健康的小鼠和改变内脏微生物环境的小鼠放在一起时,健康的小鼠患有肝病和肥胖的敏感度增加,” 论文的资深作者Richard A. Flavell说道,Richard A. Flavell是耶鲁大学医学院免疫生物学教授和霍华德休斯医学研究所研究人员的研究人员。

研究中的蛋白质被称为inflammasomes,Inflammasomes负责开启免疫系统的炎症反应,并且起到肠道细菌的传感器和调控者的作用。

耶鲁大学的团队发现小鼠体内2种特定的inflammasomes的一种成分缺乏会导致与细菌数量增加相关的微生物群落的变化。这决定了小鼠非酒精性脂肪肝(NAFLD)和肥胖的严重程度。非酒精性脂肪肝是代谢综合病症的结果、代谢综合病症是一些包括肥胖和糖尿病的疾病,是西方国家慢性肝病的主要病因。据估计,美国有超2000万人患有NAFLD。20%患有NAFLD的人发展为肝脏炎症,有患肝硬化和肝癌的风险,但起因却一直不清楚。

Flavell说,下一步把这项研究延伸到人类,更准确地鉴别出肝脏疾病发展中的有关细菌。“我们发现了靶向抗体治疗,可使小鼠身上细菌构成恢复正常,从而解除肝脏疾病。我们希望我们的研究成果最终能够为人类找到治疗方法。”(生物谷Bioon.com)

Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity

Jorge Henao-Mejia,  Eran Elinav,  Chengcheng Jin,  Liming Hao,  Wajahat Z. Mehal,  Till Strowig, Christoph A. Thaiss,  Andrew L. Kau,  Stephanie C. Eisenbarth,  Michael J. Jurczak,  Joao-Paulo Camporez,  Gerald I. Shulman,  Jeffrey I. Gordon,  Hal M. Hoffman  & Richard A. Flavell

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and the leading cause of chronic liver disease in the Western world. Twenty per cent of NAFLD individuals develop chronic hepatic inflammation (non-alcoholic steatohepatitis, NASH) associated with cirrhosis, portal hypertension and hepatocellular carcinoma, yet the causes of progression from NAFLD to NASH remain obscure. Here, we show that the NLRP6 and NLRP3 inflammasomes and the effector protein IL-18 negatively regulate NAFLD/NASH progression, as well as multiple aspects of metabolic syndrome via modulation of the gut microbiota. Different mouse models reveal that inflammasome-deficiency-associated changes in the configuration of the gut microbiota are associated with exacerbated hepatic steatosis and inflammation through influx of TLR4 and TLR9 agonists into the portal circulation, leading to enhanced hepatic tumour-necrosis factor (TNF)-α expression that drives NASH progression. Furthermore, co-housing of inflammasome-deficient mice with wild-type mice results in exacerbation of hepatic steatosis and obesity. Thus, altered interactions between the gut microbiota and the host, produced by defective NLRP3 and NLRP6 inflammasome sensing, may govern the rate of progression of multiple metabolic syndrome-associated abnormalities, highlighting the central role of the microbiota in the pathogenesis of heretofore seemingly unrelated systemic auto-inflammatory and metabolic disorders.

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