丁酸梭菌B1通过肠肝免疫调节减轻高脂饮食诱导的小鼠脂肪性肝炎。

Clostridium butyricum B1 alleviates high-fat diet-induced steatohepatitis in mice via enterohepatic immunoregulation.

作者信息

Zhou Da, Pan Qin, Liu Xiao-Lin, Yang Rui-Xu, Chen Yuan-Wen, Liu Chang, Fan Jian-Gao

机构信息

Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Medical Microbiology and Parasitology, Institutes of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

J Gastroenterol Hepatol. 2017 Sep;32(9):1640-1648. doi: 10.1111/jgh.13742.

DOI:10.1111/jgh.13742

PMID:28109017

Abstract

BACKGROUND AND AIM

Enterohepatic immunologic derangement is associated with non-alcoholic steatohepatitis. Here, we investigated whether Clostridium butyricum B1 (CB) would be an effective immune-targeted substance to attenuate steatohepatitis in mice.

METHODS

Thirty mice were randomized into a control group fed with common forage, a high-fat diet (HFD) group fed an HFD for 16 weeks, and an HFD + CB group treated with CB for the latter 8 weeks. Inflammation-associated or metabolism-associated genes in the liver or epididymal fat tissue were quantified; intrahepatic and intestinal immune factors were detected. Further short-chain fatty acids in the cecal contents or liver were measured, and differentiations of T cells in vitro were analyzed.

RESULTS

Characteristics of non-alcoholic steatohepatitis in the HFD group were obvious and were significantly attenuated in the HFD + CB group. The messenger RNA levels of monocyte chemotactic protein-1 and tumor necrosis factor-α in the liver and epididymal fat tissue were increased in the HFD group compared with the control group and were downregulated in the HFD + CB group. Intrahepatic and intestinal interferon-γ and interleukin (IL)-17 were significantly increased, whereas forkhead box P3, IL-4, and IL-22 were significantly decreased in the HFD group compared with the control group. However, these intrahepatic or intestinal immune changes were reversed after CB intervention. Furthermore, butyrate in the cecal content and liver of the HFD + CB group was significantly elevated. An in vitro investigation showed that sodium butyrate promoted CD4 T cell differentiation into Th2, Th22, or Treg, whereas it inhibited CD4 T cell differentiation into Th1 or Th17 under a cytokine milieu, which was mimicked by Trichostatin A.

CONCLUSION

Clostridium butyricum B1 could attenuate HFD-induced steatohepatitis in mice partially through butyrate-induced enterohepatic immunoregulation.

摘要

背景与目的

肠肝免疫紊乱与非酒精性脂肪性肝炎相关。在此，我们研究丁酸梭菌B1（CB）是否为减轻小鼠脂肪性肝炎的有效免疫靶向物质。

方法

将30只小鼠随机分为对照组（喂食普通饲料）、高脂饮食（HFD）组（喂食HFD 16周）和HFD + CB组（后8周用CB处理）。对肝脏或附睾脂肪组织中与炎症或代谢相关的基因进行定量；检测肝内和肠道免疫因子。进一步测量盲肠内容物或肝脏中的短链脂肪酸，并分析体外T细胞的分化情况。

结果

HFD组非酒精性脂肪性肝炎特征明显，而HFD + CB组显著减轻。与对照组相比，HFD组肝脏和附睾脂肪组织中单核细胞趋化蛋白-1和肿瘤坏死因子-α的信使核糖核酸水平升高，而在HFD + CB组中下调。与对照组相比，HFD组肝内和肠道干扰素-γ和白细胞介素（IL）-17显著增加，而叉头框P3、IL-4和IL-22显著降低。然而，CB干预后这些肝内或肠道免疫变化得以逆转。此外，HFD + CB组盲肠内容物和肝脏中的丁酸盐显著升高。体外研究表明，在曲古抑菌素A模拟的细胞因子环境下，丁酸钠促进CD4 T细胞分化为Th2、Th22或调节性T细胞，而抑制CD4 T细胞分化为Th1或Th17。