(P27-001-23) The Gut-Microbiome in Adult ADHD – A Meta-Analysis

Objectives: ADHD is a common neurodevelopmental condition that persists into adulthood in the majority of individuals. While the gut-microbiome seems to be relevant for ADHD, the literature on gut-microbial alterations in ADHD is inconsistent. These disparities might arise due to differences in the investigated phenotypes, sequencing method/region, preprocessing and statistical approaches.

Methods: To identify gut-microbiome alterations in adult ADHD that are robust over studies and statistical approaches, we harmonized bioinformatic pipelines and statistical analysis of diversity and composition of raw 16S rRNA sequencing data of four adult ADHD case-control studies (n_ADHD=312, n_Control=305). Next, we investigated differential abundance of selected genera with logistic regression and ANOVA-like Differential Expression (ALDEx2), controlling for sex and age and meta-analyzed the study results. Converging results were introduced to associations with hyperactive/impulsive and inattentive symptoms across both groups.

Results: We did not observe case-control differences in alpha diversity. Beta diversity was associated with ADHD   diagnosis but showed a significant effect of cohort, despite harmonized preprocessing, likely due to differences between studies . We further identified genera that were robustly associated with adult ADHD, e.g. Ruminococcus torques group (p_fdr=4.42x10^-2, Log odds ratio (LOR) = 0.17) was more and Eubacterium xylanophilum group (p_fdr=6.49x10^-3, LOR= -0.12) less abundant in adults with ADHD.  Eisenbergiella showed a significant association with inattentive (p_fdr=1.1x10^-3, r = 0.16) and hyperactive/impulsive (p_fdr=4.2 x 10^-3, r = 0.14) symptoms and the Ruminococcus torques group with hyperactivity/impulsivity only (p_fdr=1.2 x 10^-2, r = 0.13).

Conclusions: Those genera that were more abundant in ADHD and associated with ADHD symptoms are involved in pro-inflammatory processes and might be considered risk-conferring, while the less abundant genera in the ADHD group were related to anti-inflammatory processes.

Funding Sources: This project was supported by grants from the European Community’s Horizon 2020 Programme n° 728018 (Eat2beNICE).