目的 利用孟德尔随机化分析法探究肠道菌群与孤独症谱系障碍(ASD)的因果关联,以期为ASD患者的治疗提供新的视角。方法 采用MiBioGen公共数据库的肠道菌群GWAS数据和IEU Open GWAS数据库的ASD相关 GWAS 数据,根据预设的阈值提取与肠道菌群相对丰度显著相关的独立遗传位点作为工具变量(IVs)。主要采用逆方差加权法的效应指标优势比和95%置信区间(95%CI)对结果进行评估。使用留一法、异质性检验、水平基因多效性检验来验证结果的稳定性和可靠性。结果 Dorea(OR＝0.811, 95%CI: 0.686~0.959),Ruminiclostridium5(OR＝0.812,95%CI:0.687~0.961),RuminococcaceaeUCG005(OR＝0.776, 95%CI: 0.670~0.898),Ruminococcus1(OR＝0.831,95%CI:0.705~0.981)和Sutterella(OR＝0.821,95%CI:0.684~0.987)丰度的升高,可以降低ASD的患病风险。但是Turicibacter丰度的升高,可以增加ASD的患病风险(OR＝1.140, 95%CI: 1.008~1.290)。留一法分析显示结果稳定,不存在对结果有强影响的工具变量,且可以剔除异质性和水平基因多效性对因果效应估计产生的影响。结论 在肠道菌群中,Dorea、Ruminiclostridium5、RuminococcaceaeUCG005、Ruminococcus1和Sutterella是ASD发生的保护因素,随着菌群丰度的增加可能降低ASD的发病风险;Turicibacter是ASD发生的危险因素,随着菌群丰度的增加可能增加ASD的发病风险。
Abstract
Objective To explore the causal relationship between gut microbiota (GM) and autism spectrum disorder (ASD) by Mendelian randomization, in order to provide insight for ASD treatment. Methods GWAS data on gut microbiota from the MiBioGen public database and GWAS data on ASD from the IEU Open GWAS database were utilized. Independent genetic loci significantly associated with the relative abundance of gut microbiota were extracted as instrumental variables (IVs) based on preset thresholds. The effect size odds ratio (OR) and 95%confidence interval (CI) were primarily assessed using the inverse-variance weighted method. The stability and reliability of the results were verified using leave-one-out analysis, heterogeneity tests, and horizontal pleiotropy tests. Results Increased abundances of Dorea (OR=0.811, 95%CI: 0.686 - 0.959), Ruminiclostridium5 (OR=0.812, 95%CI: 0.687 - 0.961), RuminococcaceaeUCG005 (OR=0.776, 95%CI: 0.670 - 0.898), Ruminococcus1(OR=0.831, 95%CI: 0.705 - 0.981), and Sutterella (OR=0.821, 95%CI: 0.684 - 0.987) were associated with a decreased risk of ASD. However, an increase in Turicibacter abundance was associated with an increased risk of ASD (OR =1.140, 95%CI: 1.008 - 1.290). Leave-one-out analysis showed stable results, with no strong influential IVs, and the effects of heterogeneity and horizontal pleiotropy on causal effect estimation could be excluded. Conclusions Among gut microbiota, Dorea, Ruminiclostridium5, RuminococcaceaeUCG005, Ruminococcus1, and Sutterella are protective factors for the occurrence of ASD, and their increased abundances may reduce the incidence of ASD. In contrast, Turicibacter is a risk factor for the occurrence of ASD, and its increased abundance may increase the incidence of ASD.
关键词
肠道菌群 /
孤独症谱系障碍 /
孟德尔随机化
Key words
gut microbiota /
autism spectrum disorder /
Mendelian randomization
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基金
湖南省卫生健康委科研计划项目(B202303096080);湖南省教育厅科学研究项目(23B20063)
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