粪菌移植通过改善肠黏膜屏障功能治疗硫酸葡聚糖诱导的小鼠结肠炎

目的 研究粪菌移植(fecal microbiota transplantation,FMT)对硫酸葡聚糖(dextran sulfate sodium,DSS)诱导的溃疡性结肠炎小鼠的治疗作用.方法 将92只7周龄雌性C57 BL/6小鼠,按照随机数字表法分为4组,每组23只:对照组正常饮水,模型组饮用2％ DSS7d,在第8天时换成不含DSS的灭菌纯净水饮用7d,FMT预防组在饮用DSS建模的同时给予FMT灌胃处理,FMT治疗组在饮用7dDSS模型建成后进行FMT灌胃处理7d.记录各组小鼠体质量变化和疾病活动度,并收集每日粪便进行肠道菌群分析.在第7、14天末分别处死10只小鼠,采集血液标本进行TNF-α和D-乳酸测量,留取结肠组织分别进行HE染色、透射电镜观察,免疫组化染色检测紧密连接相关蛋白ZO-1和Occludin的表达.结果 FMT治疗组小鼠体质量、疾病活动程度和结肠长度较DSS诱导结肠炎小鼠模型组显著改善(P＜0.01).FMT治疗组血清D-乳酸和TNF-α水平较模型组明显降低(P ＜0.05,0.01).透射电镜可见FMT治疗组结肠上皮的损害及细胞间紧密连接结构和上皮完整性较模型组显著改善.FMT治疗及预防处理后ZO-1和Occludin的表达较模型组明显增高(P＜0.C5,P＜0.0I).FMT预防及治疗都能显著改善DSS引起的肠道菌群改变,促进乳杆菌属增殖而抑制拟杆菌属和颤螺菌属的生长.结论 FMT预防及治疗都能显著改善硫酸葡聚糖引起的肠道菌群改变,促进乳杆菌属增殖而抑制拟杆菌属和颤螺菌属的生长.

Fecal microbiota transplantation alleviates dextran sodium sulfate-induced colitis in mice by modulating intestinal mucosal barrier function

Objective To assess the therapeutic effect of fecal microbiota transplantation (FMT) on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) in mice.Methods A total of 92 female C57BL/6 mice (7 weeks old) were randomized into 4 equal groups,namely the normal control group (fed with normal water),DSS treatment group (model group,fed with 2％ DSS solution for 7 d followed by sterilized distilled water for another 7 d),preventive FMT group (fed with 2％ DSS solution with intragastric FMT administration for 7 d),and therapeutic FMT group (fed with 2％ DSS solution for 7 d followed by intragastric FMT administration for another 7 d).The changes in body weight and disease activity index (DAI) of the mice were recorded,and fecal samples were collected daily for 16S rRNA analysis.Ten mice from each group were sacrificed at days 7 and 14 for detection of serum levels of tumor necrosis factor-α (TNF-α) and D-lactate and pathological examination of the colon with HE staining and transmission electron microscopy.Immunohistochemistry was employed to detect the expression of ZO-1 and Occludin in the colon.Results Compared with the mice in the model group,the mice receiving therapeutic FMT showed significant improvements in body weight,DAI score and colon length (P ＜0.01) and obviously lowered serum levels of TNF-α (P ＜0.05) and D-lactate (P ＜0.01) with alleviated colonic epithelial damage and improved tight junction (TJ) and intestinal epithelial integrity.Preventive and therapeutic FMT both resulted in markedly increased expression levels of ZO-1 and Occludin in the colon compared with those in the model group (P ＜ 0.05,0.01),ameliorated the DSS-induced alteration of intestinal flora,promoted the proliferation of Lactobacillus and inhibited the growth of Bacteroides and Oscillosporic in the colon.Corcltusior FMT for both preventive and therapeutic purposes ameliorates the alteration of intestinal flora induced by DSS,promotes the proliferation of Lactobacillus and inhibits the growth of Bacteroides and Oscillosporia in the intestines of mice.