系统性红斑狼疮小鼠肠道微生物与抗dsDNA抗体水平的相关性

Correlation between gut microbiota and anti-dsDNA antibody in the mouse model of systemic lupus erythematosus

目的探讨系统性红斑狼疮(简称狼疮)TC小鼠肠道微生物菌群结构与抗ds DNA抗体之间的关系。方法 ELISA法检测狼疮TC小鼠血清抗ds DNA抗体,然后分别收集ds DNA阳性组和阴性组的小鼠粪便,利用Illumina Hi Seq 2500高通量测序,进行粪便样本16S测序,比较两组之间的肠道微生物菌群结构与抗ds DNA抗体水平之间的关系。结果通过ELISA检测抗体结果和小鼠粪便高通量测序结果显示,ds DNA阳性组TC小鼠的物种群落多样性显著低于ds DNA阴性组;同时,两组TC小鼠肠道微生物分别在门水平Chloroflexi(绿弯菌门);纲水平Betaproteobacteria(β变形菌纲)、Deltaproteobacteria(δ变形菌纲)和Ktedonobacteria(纤线杆菌纲);目水平Burkholderiales(伯克氏菌目)、Desulfovibrionales(脱硫弧菌目)和Ktedonobacterales(纤线杆菌目);科水平Alcaligenaceae(产碱菌科)和Desulfovibrionaceae(脱硫弧菌科);属水平Parasutterella(副萨特氏菌属)和Desulfovibrio(脱硫弧菌属)上差异有显著性(P<0.05)。结论狼疮TC小鼠肠道微生物菌群结构与抗ds DNA抗体高度相关,本研究为进一步阐明肠道微生物菌群与系统性红斑狼疮发病机制的关系提供依据。

Objective To explore the relationship between gut microbiota and anti-dsDNA antibody in systemic lupus erythematosus(lupus)TC mice.Methods ELISA was performed to detect serum anti-dsDNA antibody in the lupus TC mice.Then,the feces of both dsDNA-positive and-negative mice were collected,and 16S rRNA of the stool sample was sequenced by Illumina HiSeq 2500 high-throughput sequencing,to analyze the relationship between gut microbiota and anti-dsDNA antibody level in the two groups.Results The result of ELISA and mouse fecal high-throughput sequencing showed that the species diversity of gut microbiota in the dsDNA-positive TC mice was significantly lower than that in the dsDNA-negative TC mice.The gut microbiota of TC mice in the two groups showed significant differences at different classification levels:Chloroflexi at phylum level,Betaproteobacteria,Deltaproteobacteria and Ktedonobacteria at class level,Burkholderiales,Desulfovibrionales and Ktedonobacterales at order level,Alcaligenaceae and Desulfovibrionaceae at family level,and Parasutterella and Desulfovibrio at genus level(P<0.05 for all).Conclusions The flora composition of gut microbiota in lupus TC mice is highly correlated with anti-dsDNA antibody.The results of our study provide a basis for further elucidation of the relationship between gut microbiota and the pathogenetic mechanism of systemic lupus erythematosus.