The Role of Leaky Gut in Nonalcoholic Fatty Liver Disease: A Novel Therapeutic Target.
The Role of Leaky Gut in Nonalcoholic Fatty Liver Disease: A Novel Therapeutic Target.
复制标题
肠漏在非酒精性脂肪性肝病中的作用：一个新的治疗靶点
DOI：
10.3390/ijms22158161
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发表时间：
2021-07-29
影响因子：
5.6
通讯作者：
Nakajima A
中科院分区：
文献类型：
--
作者：
Kessoku T;Kobayashi T;Tanaka K;Yamamoto A;Takahashi K;Iwaki M;Ozaki A;Kasai Y;Nogami A;Honda Y;Ogawa Y;Kato S;Imajo K;Higurashi T;Hosono K;Yoneda M;Usuda H;Wada K;Saito S;Nakajima A
肝脏直接接受肠道的血液，因此暴露在肠道细菌中。最近的研究表明，肠道细菌与非酒精性脂肪性肝病(NAFLD)之间存在关系。近10-20%的NAFLD患者发展为非酒精性脂肪性肝炎(NASH)，革兰氏阴性杆菌产生的内毒素可能参与了NAFLD的发病。NAFLD高内毒素血症有肠道和肝脏因素。肠道因素包括肠道屏障功能受损(肠漏综合征)，以及由于产生乙醇的细菌数量增加而导致的生物失调，这可能会改变内源性酒精浓度。肝脏因素包括高瘦素血症，这与内毒素的过度反应有关，导致肝内炎症和纤维化。临床上，一些益生菌和其他药物的随机对照试验针对肠道细菌和NAFLD之间的关系进行了研究，但结果并不一致。最近的一项随机、安慰剂对照研究探索了治疗便秘的鲁比前列酮在恢复肠道屏障功能和改善NAFLD患者预后方面的效用，标志着针对肠道屏障的新疗法的开发进入了一个新阶段。本文综述了动物模型研究和随机临床试验中有关肠-肝轴在NAFLD发病和发展中的作用的最新数据。
The liver directly accepts blood from the gut and is, therefore, exposed to intestinal bacteria. Recent studies have demonstrated a relationship between gut bacteria and nonalcoholic fatty liver disease (NAFLD). Approximately 10–20% of NAFLD patients develop nonalcoholic steatohepatitis (NASH), and endotoxins produced by Gram-negative bacilli may be involved in NAFLD pathogenesis. NAFLD hyperendotoxicemia has intestinal and hepatic factors. The intestinal factors include impaired intestinal barrier function (leaky gut syndrome) and dysbiosis due to increased abundance of ethanol-producing bacteria, which can change endogenous alcohol concentrations. The hepatic factors include hyperleptinemia, which is associated with an excessive response to endotoxins, leading to intrahepatic inflammation and fibrosis. Clinically, the relationship between gut bacteria and NAFLD has been targeted in some randomized controlled trials of probiotics and other agents, but the results have been inconsistent. A recent randomized, placebo-controlled study explored the utility of lubiprostone, a treatment for constipation, in restoring intestinal barrier function and improving the outcomes of NAFLD patients, marking a new phase in the development of novel therapies targeting the intestinal barrier. This review summarizes recent data from studies in animal models and randomized clinical trials on the role of the gut–liver axis in NAFLD pathogenesis and progression.
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影响因子：
3.7
作者：
Baker SS;Baker RD;Liu W;Nowak NJ;Zhu L
通讯作者：
Zhu L
影响因子：
7.7
作者：
Cani, Patrice D.;Amar, Jacques;Burcelin, Remy
通讯作者：
Burcelin, Remy
影响因子：
3.7
作者：
Arakawa, Kentaro;Ishigami, Tomoaki;Tamura, Kouichi
通讯作者：
Tamura, Kouichi
影响因子：
4.2
作者：
Esposito, Emanuela;Iacono, Anna;Meli, Rosaria
通讯作者：
Meli, Rosaria
DOI：
10.1016/0024-3205(71)90194-9
发表时间：
1971-01-01
期刊：
LIFE SCIENCES PT-2 BIOCHEMISTRY GENERAL AND MOLECULAR BIOLOGY
影响因子：
--
作者：
BLOMSTRAND, R
通讯作者：
BLOMSTRAND, R