Small intestinal bacterial overgrowth and toll-like receptor signaling in patients with non-alcoholic fatty liver disease
Small intestinal bacterial overgrowth and toll-like receptor signaling in patients with non-alcoholic fatty liver disease
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DOI：
10.1111/jgh.13058
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发表时间：
2016-01-01
影响因子：
4.1
通讯作者：
Chawla, Yogesh
中科院分区：
文献类型：
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作者：
Kapil, Shweta;Duseja, Ajay;Chawla, Yogesh
背景和目的：非酒精性脂肪性肝病（NAFLD）的发病机制是多因素的。关于小肠细菌过度生长（SIBO）和Toll样受体（TLR）信号传导在NAFLD中的作用的文献很少。本研究评估了NAFLD患者SIBO与TLR信号基因表达的关系。共142例受试者由NAFLD组成（n = 60，平均年龄38.7 ± 10.4岁），慢性病毒性肝炎（CVH）研究中招募了32名健康志愿者（n = 32，平均年龄39.5 +/-10.6岁）和50名健康志愿者（n = 50，平均年龄36.56 +/-4.2岁）。在32例前瞻性NAFLD患者中，通过内窥镜采集十二指肠液以评估SIBO。采用RT-PCR和免疫组织化学方法分别检测了64例患者（NAFLD= 32例，CVH= 32例）肝脏TLR 4、CD 14、TLR 2、NF-κ β和MD 2的mRNA表达以及TLR 4和TLR 2的蛋白表达。血清TNF-α，脂联素，胰岛素和内毒素水平也evaluated.Results：小肠细菌过度生长存在于12（37.5%）的32例NAFLD与大肠杆菌为优势菌。与无SIBO的患者相比，SIBO患者的内毒素水平显著升高，CD 14 mRNA、核因子κ β mRNA和TLR 4蛋白表达显著升高。与非NASH患者相比，NASH患者具有显著更高的内毒素水平和更高的TLR 4蛋白表达强度。血清中TNF-α，内毒素，胰岛素水平显着较高，脂联素较低，在NAFLD与CVH和健康volunteers.Conclusions相比：我们的研究提供了第一个直接证据的作用SIBO和内毒素血症及其与TLR信号基因和肝脏组织学NAFLD患者。
Background and Aim: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is multifactorial. There is sparse literature on the role of small intestinal bacterial overgrowth (SIBO) and toll-like receptor (TLR) signaling in NAFLD. The present study evaluated the relationship of SIBO with expression of TLR signaling genes in patients with NAFLD.Methods: A total of 142 subjects composed of NAFLD (n = 60, mean age 38.7 +/- 10.4 years), chronic viral hepatitis (CVH) (n = 32, mean age 39.5 +/- 10.6 years), and healthy volunteers (n = 50, mean age 36.56 +/- 4.2 years) were enrolled in the study. Duodenal fluid was taken endoscopically in 32 prospective patients with NAFLD for evaluation of SIBO. Hepatic mRNA expression of TLR4, CD14, TLR2, NF-kappa beta, and MD2 and protein expression of TLR4 and TLR2 were studied in 64 patients (NAFLD= 32, CVH= 32) by RT-PCR and immunohistochemistry, respectively. Serum levels of TNF-alpha, adiponectin, insulin, and endotoxins were also evaluated.Results: Small intestinal bacterial overgrowth was present in 12 (37.5%) out of 32 patients with NAFLD with Escherichia coli as the predominant bacterium. In comparison with those without SIBO, patients with SIBO had significantly higher endotoxin levels and higher CD14 mRNA, nuclear factor kappa beta mRNA, and TLR4 protein expression. Patients with NASH had significantly higher endotoxin levels and higher intensity of TLR4 protein expression in comparison with patients without NASH. Serum levels of TNF-alpha, endotoxins, and insulin were significantly higher and of adiponectin lower in NAFLD in comparison with CVH and healthy volunteers.Conclusions: Our study provides the first direct evidence of role of SIBO and endotoxemia and its relation with TLR signaling genes and liver histology in patients with NAFLD.