抗生素诱导的肠道菌群失调加重小鼠肺炎支原体感染

Antibiotic-induced gut microbiota dysbiosis aggravates Mycoplasma pneumoniae infection

目的初步探讨抗生素诱导的肠道菌群失调对肺炎支原体(Mycoplasma pneumoniae,Mp)呼吸道感染的影响。方法C57BL/6J小鼠口服万古霉素和庆大霉素21 d后滴鼻感染Mp。实时荧光定量PCR(qPCR)分析抗生素处理前后小鼠粪便中5个主要菌门的菌量;qPCR检测感染后3 d和7 d肺组织中Mp载量;病理切片和HE染色分析肺组织炎症病理改变;流式细胞术分析小鼠脾脏T淋巴细胞分泌的IFN-γ和IL-4;间接ELISA检测Mp特异性IgM和IgG。结果口服万古霉素和庆大霉素后小鼠粪便中拟杆菌门菌量显著减少,厚壁菌门菌量增多,δ,γ变形杆菌门、放线菌门和软壁菌门菌量亦发生改变;口服抗生素小鼠感染Mp后3 d和7 d肺组织Mp载量和炎症病理评分增加,7 d小鼠脾淋巴细胞中分泌IFN-γ的CD4+T细胞减少。结论抗生素诱导的小鼠肠道菌群失调可加重Mp呼吸道感染。

Objective To investigate the influences of antibiotic-induced gut microbiota dysbiosis on Mycoplasma pneumoniae(Mp)airway infection.Methods C57BL/6J mice were treated with vancomycin and gentamicin for 21 d by oral delivery and then intranasally infected with Mp.Quantitative real-time PCR(qPCR)was performed to detect five major phyla of gut microbiota in mouse fecal specimens before and after antibiotic treatment and the loads of Mp in lung tissues on 3 d and 7 d after infection.Pathological changes in lung tissues were evaluated with HE staining.IFN-γand IL-4 secreted by spleen CD4+T cells and CD8+T cells were analyzed by flow cytometry.Mp-specific IgM and IgG in mouse serum samples were measured by indirect enzyme-linked immunosorbent assay(ELISA).Results Vancomycin and gentamicin treatment significantly reduced the number of Bacteroidetes in mouse feces,but increased the amount of Firmicutes.Meanwhile,the numbers ofδ,γ-Proteobacteria,Actinomycetes and Tenericutes also changed.These antibiotic-induced gut microbiota alterations in mice with Mp infection increased the loads of Mp in lung tissues and the pathological scores of lung tissue inflammation on 3 d and 7 d after infection,and reduced the number of IFN-γ-secreting spleen CD4+T lymphocytes on 7 d.Conclusions Antibiotic-induced gut microbiota dysbiosis aggravated Mp airway infection.