Mendelian randomization analysis on the association between gut microbiota and attention deficit/hyperactivity disorder with autism spectrum disorder

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.

Keywords

gut microbiota / Mendelian randomization / attention-deficit/hyperactivity disorder / autism spectrum disorder / causality