芬氏另枝菌促进炎症性肠病发展及其机制
作者:
作者单位:

1.南方医科大学 南方医院,广东 广州;2.军事医学研究院,病原微生物与生物安全全国重点实验室,北京;3.安徽医科大学 基础医学院,安徽 合肥

作者简介:

郝自创:完成实验并编写论文;李东:参与协助实验操作;童江辉:参与协助实验操作;覃小铭:参与协助实验操作;张欢:参与协助实验操作、数据分析和论文讨论;王雅婧:参与协助实验操作;杨瑞馥:参与实验方案的设计并对论文撰写和修改提出相关意见;谭亚芳:参与实验方案的设计并对论文撰写和修改提出相关意见;毕玉晶:参与实验的研究构思和设计,并参与文章的修改;智发朝:参与实验的研究构思和设计,并参与文章的修改。

基金项目:

国家自然科学基金(82172729);广东省胃肠疾病重点实验室项目(2017B030314037)


Alistipes finegoldii promotes the development of inflammatory bowel disease: effect and mechanism
Author:
Affiliation:

1.Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China;2.State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, China;3.School of Basic Medical Sciences, Anhui Medical University, Hefei, Anhui, China

Fund Project:

This work was supported by the National Natural Science Foundation of China (82172729) and the Guangdong Provincial Key Laboratory of Gastroenterology Project (2017B030314037).

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    摘要:

    目的 探究芬氏另枝菌(Alistipes finegoldii)对炎症性肠病(inflammatory bowel disease, IBD)的影响,并进一步阐明其潜在的相关致病机制。方法 6周龄的雄性C57BL/6J小鼠在饮用链霉素3 d后,被随机分为3组:对照组(Control组)、PBS组和给菌组(AF组)。通过灌胃给予芬氏另枝菌(每只1×109 CFU/200 μL)或PBS,持续2周。之后,小鼠饮用含有2.5%葡聚糖硫酸钠(dextran sulfate sodium, DSS)的水溶液1周以诱导结肠炎模型。评估小鼠的体重下降分数、粪便性状、血便情况、结肠长度,对结肠组织进行HE染色并进行组织病理评分;于实验开始及结束时收集小鼠粪便,进行16S rRNA基因扩增子测序;用实时定量聚合酶链式反应(qPCR)检测结肠组织相关肠屏障蛋白和炎症因子的mRNA表达。结果 AF组小鼠的体重下降分数、疾病活动度指数评分、结肠缩短程度及组织病理评分均高于PBS组。肠屏障的紧密连接蛋白Occludin、Claudin 5的mRNA表达相较于PBS组下降,而炎症因子IL-17A的mRNA表达则升高。AF组相较于PBS组的肠道菌群α多样性降低;β多样性分析显示两组间肠道菌群多样性存在显著性差异。线性判别分析效应大小(linear discriminant analysis effect size, LEfSe)分析发现,给菌组与PBS组之间存在显著差异的细菌类群: 在纲水平上,芽孢杆菌纲 (Bacilli);在目水平上,丹毒丝菌目(Erysipelotrichales);在科水平上,丹毒丝菌科(Erysipelotrichaceae)、海生线状菌科(Marinifilaceae);在属水平上,气杆菌属(Odoribacter)、杜博斯氏菌属(Dubosiella);在种水平上,纽约杜博斯氏菌(Dubosiella newyorkensis),在给菌组中显著高于PBS组。结论 芬氏另枝菌能够促进炎症因子的分泌,损害肠黏膜通透性,改变肠道菌群的结构和多样性,从而加剧肠炎的发展。

    Abstract:

    Objective To study the effect of Alistipes finegoldii (AF) on inflammatory bowel disease (IBD) and the underlying mechanism.Methods Six-week-old male C57BL/6J mice were administrated with streptomycin for three days and then randomly assigned into the control, phosphate buffered saline (PBS), and AF groups. Mice were administrated with AF suspension (1×109 CFU, 200 μL per mouse) or PBS by gavage for two weeks, followed by drinking of the water containing 2.5% dextran sulfate sodium (DSS) for one week for the modeling of colitis. The weight loss fraction percentage, fecal characteristics, blood fecesstools, and colon length were determined. The colon tissue was stained with hematoxylin-eosin for the scoring of histopathological changes, and feces samples were collected at the beginning and end of the experiment for sequencing of 16S rRNA gene amplicons at the beginning and end of the experiment. The mRNA levels of colon tissue-associated intestinal barrier proteins and inflammatory mediators were determined by qPCR.Results The mice in the AF group had severer disease conditions than those in the PBS group regarding the weight loss percentage, disease activity index, colon shortening, and histopathological score. Compared with the PBS group, the AF group showed down-regulated mRNA levels of occludin and claudin 5 and up-regulated mRNA level of interleukin (IL)-17A. The AF group had lower alpha diversity of intestinal flora than the PBS group, and the beta diversity showed significant differences between AF and PBS groups. The linear discriminant analysis effect size (LEfSe) results revealed that the significantly differential bacteria between AF and PBS groups were Bacilli, Erysipelotrichales, Erysipelotichaceae, Odoribacter, Marinifilaceae, Dubosiella, and Dubosiella newyorkensis.Conclusion AF promotes the secretion of inflammatory mediators, impairs the permeability of the intestinal mucosa, and alters the structure and diversity of the intestinal flora, thereby promoting the development of IBD.

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郝自创,李东,童江辉,覃小铭,张欢,王雅婧,杨瑞馥,谭亚芳,毕玉晶,智发朝. 芬氏另枝菌促进炎症性肠病发展及其机制[J]. 微生物学报, 2025, 65(3): 1108-1118

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  • 收稿日期:2024-11-12
  • 在线发布日期: 2025-03-10
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