目的 采用孟德尔随机化评估肠道菌群(GM)与注意缺陷多动障碍(ADHD)以及孤独症谱系障碍(ASD)之间的潜在因果关系。方法 利用全基因组关联分析(GWAS)公共数据进行双样本MR分析,探讨肠道菌群与ADHD、ASD之间的关系。据预设的阈值(P＜10-5)提取与211种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)。采用逆方差加权法等多种方法进行分析,根据效应指标优势比(OR)和95%置信区间(95%CI)评估结果。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 脱硫弧菌属(Desulfovibrio)、紫单胞菌科(Porphyromonadaceae)、厚壁菌门(Firmicutes)丰度的升高可以降低ADHD的患病风险,其优势比与置信区间分别为:OR=0.742 (95%CI:0.595～0.925)、OR=0.761 (95%CI:0.585～ 0.989)、OR=0.799 (95%CI:0.646～ 0.988),而双歧杆菌目((Bifidobacteriales)为ADHD的潜在危险性因素,其丰度的增高会增加ADHD的患病风险(OR=1.335,95%CI:1.111～ 1.605);瘤胃球菌属(Ruminococcus)、革兰氏阴性杆细菌(Gram negative bacillus)、革兰氏阳性厌氧菌(Gram Positive bacillus)丰度升高可以降低ASD的患病风险,其优势比与置信区间分别为:OR=0.778 (95％CI:0.671～0.901)、OR=0.821 (95％CI:0.684～0.987)、OR=0.811 (95％CI:0.686～0.959),普雷沃氏菌属(Prevonella)丰度升高会增加ASD的患病风险(OR=1.238,95％CI:1.091～1.404)。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 肠道菌群与ADHD和ASD之间存在潜在联系,并提供可供进一步研究的菌群信息,具有重要意义。
Abstract
Objective To analyze the potential causal relationship between gut microbiota (GM) and two common neurodevelepmentcoldisorders, attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) using Mendelian randomization (MR). Methods A two-sample MR analysis was conducted using publicly available genome-wide association study (GWAS) data to explore the relationship between gut microbiota and ADHD/ASD. Independent genetic loci significantly associated with the relative abundance of 211 gut microbiota taxa were selected as instrumental variables (IVs) based on a predefined threshold (P<10-5). Multiple methods, including the inverse-variance weighted (IVW) method, were employed for analysis, with results evaluated using odds ratios (ORs) and 95% confidence intervals (CIs). Sensitivity analysis, including leave-one-out analysis, heterogeneity testing, and horizontal pleiotropy testing, were performed to ensure the stability and reliability of the results. Results Increased abundance of Desulfovibrio (OR=0.742, 95%CI: 0.595 - 0.925), Porphyromonadaceae (OR＝0.761, 95%CI: 0.585 - 0.989), and Firmicutes (OR＝0.799, 95%CI: 0.646 - 0.988) was associated with a reduced risk of ADHD. In contrast, increased abundance of Bifidobacteriales was identified as a potential risk factor for ADHD (OR＝1.335, 95%CI: 1.111 - 1.605). For ASD, increased abundance of Ruminococcus (OR＝0.778, 95%CI: 0.671 - 0.901), Gram-negative bacillus (OR＝0.821, 95% CI: 0.684 - 0.987), and Gram-positive anaerobic bacteria (OR＝0.811, 95%CI: 0.686 - 0.959) was associated with a reduced risk, while increased abundance of Prevotella was associated with an increased risk of ASD (OR＝1.238, 95%CI: 1.091 - 1.404). Leave-one-out analysis confirmed the stability of the results, with no strong influential IVs detected. Heterogeneity and horizontal pleiotropy were ruled out as confounding factors. Conclusions This study demonstrates a potential causal link between gut microbiota and two common childhood psychiatric disorders, ADHD and ASD. It provides valuable insights into specific microbial taxa that may influence disease risk, offering a foundation for further research and potential therapeutic targets.
关键词
肠道菌群 /
孟德尔随机化 /
注意缺陷多动障碍 /
孤独症谱系障碍 /
因果关系
Key words
gut microbiota /
Mendelian randomization /
attention-deficit/hyperactivity disorder /
autism spectrum disorder /
causality
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