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内毒素血症在小儿非酒精性脂肪性肝炎发病机制中并非必需。

Endotoxemia unrequired in the pathogenesis of pediatric nonalcoholic steatohepatitis.

作者信息

Yuan Jianye, Baker Susan S, Liu Wensheng, Alkhouri Razan, Baker Robert D, Xie Jianqun, Ji Guang, Zhu Lixin

机构信息

Digestive Diseases and Nutrition Center, Department of Pediatrics, The State University of New York at Buffalo, Buffalo, New York, USA; Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

出版信息

J Gastroenterol Hepatol. 2014 Jun;29(6):1292-8. doi: 10.1111/jgh.12510.

DOI:10.1111/jgh.12510
PMID:24372861
Abstract

BACKGROUND AND AIM

Nonalcoholic steatohepatitis (NASH), the severe form of nonalcoholic fatty liver disease, is a serious liver complication associated with obesity. Several studies suggest that endotoxemia is associated with nonalcoholic fatty liver disease and NASH. We aimed to study the correlation of gut microbiome composition and the incidence of endotoxemia in obese patients and NASH patients in comparison with normal controls.

METHODS

The abundance of Gram-negative bacteria in the gut microbiomes of normal controls, obese patients with normal liver, and biopsy-proven NASH patients were assessed using 16S rRNA pyrosequencing data. Serum endotoxin was determined by endpoint limulus amebocyte lysate assay.

RESULTS

Higher abundance of Gram-negative bacteria in gut microbiome was observed in obese and NASH patients in comparison with normal controls, but no difference was detected between obese and NASH patients. Serum endotoxin is higher in the NASH group than the normal controls. In addition, the obese and NASH patients had a higher incidence of endotoxemia compared with normal controls. However, Spearman's test found no correlation between the abundance of Gram-negative bacteria and serum endotoxin levels. The majority of the NASH patients and the obese patients had low serum endotoxin level. Among NASH patients, serum endotoxin is not correlated with disease severity.

CONCLUSIONS

Our data suggest that the gut microbiome composition does not contribute to the incidence of endotoxemia in NASH, and endotoxemia is not required in the pathogenesis of NASH. Our observations highlight the current concept that multiple factors contribute to the development of NASH.

摘要

背景与目的

非酒精性脂肪性肝炎(NASH)是非酒精性脂肪性肝病的严重形式,是一种与肥胖相关的严重肝脏并发症。多项研究表明,内毒素血症与非酒精性脂肪性肝病及NASH相关。我们旨在研究肥胖患者和NASH患者肠道微生物群组成与内毒素血症发生率之间的相关性,并与正常对照进行比较。

方法

使用16S rRNA焦磷酸测序数据评估正常对照、肝脏正常的肥胖患者以及经活检证实的NASH患者肠道微生物群中革兰氏阴性菌的丰度。通过终点鲎试剂法测定血清内毒素。

结果

与正常对照相比,肥胖患者和NASH患者肠道微生物群中革兰氏阴性菌的丰度更高,但肥胖患者与NASH患者之间未检测到差异。NASH组血清内毒素水平高于正常对照。此外,与正常对照相比,肥胖患者和NASH患者内毒素血症的发生率更高。然而,Spearman检验发现革兰氏阴性菌的丰度与血清内毒素水平之间无相关性。大多数NASH患者和肥胖患者血清内毒素水平较低。在NASH患者中,血清内毒素与疾病严重程度无关。

结论

我们的数据表明,肠道微生物群组成与NASH内毒素血症的发生率无关,且NASH的发病机制中不需要内毒素血症。我们的观察结果强调了当前的概念,即多种因素促成了NASH的发生发展。

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