2018 年第 7 期 第 13 卷

功能性胃肠病患者中肠道菌群与脑源性神经营养因子及紧密连接蛋白ZO1表达的相关性分析

Relation among intestinal flora, expressions of brain-derived neurotrophic factor and tight junction protein ZO1 in patients with functional gastrointestinal disorder

作者：王慕董丽娜张芳王俊平李才华

英文作者：

单位：030012太原，山西省人民医院神经内科（王慕），中心实验室（董丽娜、张芳），消化内科（王俊平）；200120上海天昊生物科技有限公司（李才华）

英文单位：

关键词：功能性胃肠病；脑源性神经营养因子；肠道菌群

英文关键词：

• 摘要：

• 【摘要】目的    分析功能性胃肠病患者中肠道菌群与脑源性神经营养因子（BDNF）及紧密连接蛋白ZO1表达的相关性。方法    选取山西省人民医院消化科2014年8月至2015年3月诊断为功能性胃肠病行肠镜检查患者32例，同时收集粪便和结肠黏膜标本，提取粪便和黏膜组织DNA后，对16S rRNA基因的V3～V4区进行高通量测序。使用实时荧光定量聚合酶链反应方法检测BDNF和ZO1的mRNA表达量，并应用生物信息学方法比较粪便和黏膜菌群差异，并对粪便、黏膜菌群与BDNF和ZO1表达量的相关性进行分析。结果    在属水平，许多菌的丰度在粪便菌群和黏膜菌群中存在显著差异。在种水平，十几种菌与BDNF的表达量显著负相关，而另外也有十几种菌与ZO1的表达量呈显著正相关。粪便和黏膜与同一蛋白相关的菌种不同。粪便中的Gardnerella_vaginalis和Sutterella_sp._252菌以及黏膜中的Bacteroides vulgatus， uncultured Ruminococcus sp.， uncultured bacterium adhufec236， bacterium Shr3， uncultured bacterium adhufec77.25与BDNF和ZO1同时存在显著的相关性。粪便中与BDNF呈负相关的菌株butyrate-producing bacterium_GM2/1和Bifidobacterium_longum在黏膜中与ZO1表达呈显著正相关。结论    功能性胃肠病患者中多个菌株与BDNF负相关的同时与ZO1正相关，有可能成为同时调控BDNF和ZO1表达的备选菌种用于功能性胃肠病的治疗。

• 【Abstract】Objective    To analyze the relation among intestinal flora, expressions of brain-derived neurotrophic factor（BDNF） and tight junction protein ZO1 in patients with functional gastrointestinal disorder. Methods    Thirty-two patients with functional gastrointestinal disorder undergoing enteroscopy from August 2014 to March 2015 in Shanxi Provincial People′s Hospital were enrolled. Specimens of feces and colonic mucosa were collected to extract DNA; high-throughput sequencing of the V3-V4 region of 16S rRNA was performed. Expressions of BDNF and ZO1 mRNA in feces and colonic mucosa were detected by the real-time fluorescence quantitative polymerase chain reaction. Bacterial flora distribution of feces and colonic mucosa was observed using bioinformatics method. The relation among flora distribution, expressions of BDNF and ZO1 was analyzed. Results    Abundance count of bacteria at genus level showed significant differences among specimens of fecal flora and colonic mucosal flora. At species level, over a dozen of strains of bacteria were negatively related to BDNF expression; many strains of bacteria were positively related to ZO1 expression. Gardnerella vaginalis and Sutterella_sp._252 in feces, Bacteroides vulgatus, uncultured Ruminococcus sp., uncultured bacterium adhufec236, bacterium Shr3 and uncultured bacterium adhufec77.25 in mucosa were correlated with both BDNF and ZO1 expression. Butyrate-producing bacterium_GM2/1 and Bifidobacterium_longum were negatively related to BDNF expression in feces but positively related to ZO1 expression in mucosa. Conclusions    ome strains of bacteria are correlated with both BDNF and ZO1 in patients with functional gastrointestinal disorder; the strains provide a new choice for the treatment of functional gastrointestinal disorder.

  【Key words】Functional gastrointestinal disorders;Brain-derived neurotrophic factor;Intestinal flora

  【Fund program】Scientific Research Project of Health and Family Planning Commission of Shanxi Province(201601014, 2017020)