粪菌移植对哮喘幼鼠气道炎症的影响及其机制

Effect and mechanism of fecal microbiota transplantation on allergic airway inflammation in young asthma mice

目的探讨粪菌移植对过敏性哮喘幼鼠的影响及其机制。方法孕2周的BALB/c小鼠随机分为三组:正常对照组,哮喘模型组和粪菌移植组。待幼鼠出生后,模型组和粪菌移植组通过卵清蛋白(OVA)致敏(第0天、第7天和第14天)及激发(第21-28天)建立哮喘幼鼠模型;粪菌移植组于生后第21-28天给予粪菌混悬液灌胃;对照组均采用生理盐水干预。在末次激发24 h后,检测三组幼鼠的气道高反应性、肺组织病理学变化、肺泡灌洗液(BALF)中白细胞分类和炎性因子IL-4、IL-5、IL-13表达水平及肺组织调节性T细胞(Tregs)的含量。结果与模型组比较,粪菌移植组幼鼠的气道高反应性显著降低(P<0.05);病理染色显示气道炎症细胞浸润程度明显减轻;BALF中白细胞总数、嗜酸粒细胞和中性粒细胞明显下降(P<0.001),IL-4、IL-5和IL-13水平显著降低(P<0.0001或P<0.01);并且幼鼠肺组织中Tregs/CD4^(+)T细胞比例显著提高(P<0.05)。结论粪菌移植通过诱导Tregs的增生抑制哮喘幼鼠的气道炎症,对哮喘起到治疗作用。

Objective To explore the effect of fecal microbiota transplantation(FMT)on allergic airway inflammation in young asthmatic mice and its mechanism.Methods BALB/c mice with pregnancy for 2 weeks were randomly divided into three groups:normal control group,asthma group(OVA group)and fecal microbiota transplantation group(FMT+OVA group).The neonatal mice in OVA group and FMT+OVA group were sensitized(at day 0,7,14 after birth)and challenged(at day 21-28 after birth)with ovalbumin(OVA)to establish young mouse models of allergic asthma,neonatal mice in FMT+OVA group were treated with fecal microbiota transplantation by gavage from day 21 to day 28 after birth,and neonatal mice in control group were given normal saline.Twenty-four hours after the last challenge,the airway hyperreactivity(AHR)was detected,the lung tissues were stained,and the total number of WBC and differential inflammatory cell number,the concentrations of IL-4,IL-5 and IL-13 in BALF,and the changes of regulatory T cells(Tregs)were detected.Results Compared with OVA group,the AHR of mice was significantly decreased in FMT+OVA group(P<0.05),the infiltration of airway inflammatory cells was significantly reduced in lung tissue,the numbers of total inflammatory cells,eosinophils and neutrophils were significantly decreased(P<0.001)and the levels of IL-4,IL-5 and IL-13 in BALF were significantly decreased(P<0.0001 or P<0.01),and the proportion of Tregs/CD4^(+)T cells in lung was significantly increased(P<0.05).Conclusion FMT could ameliorate the allergic airway inflammation of asthmatic neonatal mice by inducing the promotion of Tregs,which suggests that FMT might have therapeutic effects on asthma.