肠道菌群与注意缺陷多动障碍和孤独症谱系障碍的孟德尔随机化分析

doi:10.11852/zgetbjzz2024-1270

摘要/Abstract

摘要： 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。

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

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.

Key words: gut microbiota, Mendelian randomization, attention-deficit/hyperactivity disorder, autism spectrum disorder, causality

中图分类号:

R179

姜含笑, 乔艺, 屈艳琳. 肠道菌群与注意缺陷多动障碍和孤独症谱系障碍的孟德尔随机化分析[J]. 中国儿童保健杂志, 2025, 33(7): 707-714.

JIANG Hanxiao, QIAO Yi, QU Yanlin. Mendelian randomization analysis on the association between gut microbiota and attention deficit/hyperactivity disorder with autism spectrum disorder[J]. Chinese Journal of Child Health Care, 2025, 33(7): 707-714.

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