1. The gut-microbiome in adult Attention-deficit/hyperactivity disorder - A Meta-analysis.
- Author
-
Jakobi B, Vlaming P, Mulder D, Ribases M, Richarte V, Ramos-Quiroga JA, Tendolkar I, van Eijndhoven P, Vrijsen JN, Buitelaar J, Franke B, Hoogman M, Bloemendaal M, and Arias-Vasquez A
- Abstract
Attention-deficit/hyperactivity disorder (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 few publications on gut-microbial alterations in ADHD are inconsistent, in the investigated phenotypes, sequencing method/region, preprocessing, statistical approaches, and findings. To identify gut-microbiome alterations in adult ADHD, robust across studies and statistical approaches, we harmonized bioinformatic pipelines and analyses of raw 16S rRNA sequencing data from four adult ADHD case-control studies (N
ADHD =312, NNoADHD =305). We investigated diversity and differential abundance of selected genera (logistic regression and ANOVA-like Differential Expression tool), corrected for age and sex, and meta-analyzed the study results. Converging results were investigated for association with hyperactive/impulsive and inattentive symptoms across all participants. Beta diversity was associated with ADHD diagnosis but showed significant heterogeneity between cohorts, despite harmonized analyses. Several genera were robustly associated with adult ADHD; e.g., Ruminococcus_torques_group (LogOdds=0.17, pfdr =4.42 × 10-2 ), which was more abundant in adults with ADHD, and Eubacterium_xylanophilum_group (LogOdds= -0.12, pfdr =6.9 × 10-3 ), which was less abundant in ADHD. Ruminococcus_torques_group was further associated with hyperactivity/impulsivity symptoms and Eisenbergiella with inattention and hyperactivity/impulsivity (pfdr <0.05). The literature points towards a role of these genera in inflammatory processes. Irreproducible results in the field of gut-microbiota research, due to between study heterogeneity and small sample sizes, stress the need for meta-analytic approaches and large sample sizes. While we robustly identified genera associated with adult ADHD, that might overall be considered beneficial or risk-conferring, functional studies are needed to shed light on these properties., Competing Interests: Declaration of competing interest J.A.R.Q was on the speakers’ bureau and/or acted as consultant for Biogen, Janssen-Cilag, Novartis, Shire, Takeda, Bial, Shionogi, Sincrolab, Novartis, BMS, Medice, Rubió, Uriach, Technofarma and Raffo in the last 3 years. He also received travel awards (air tickets + hotel) for taking part in psychiatric meetings from Janssen-Cilag, Rubió, Shire, Takeda, Shionogi, Bial and Medice. The Department of Psychiatry chaired by him received unrestricted educational and research support from the following companies in the last 3 years: Janssen- Cilag, Shire, Oryzon, Roche, Psious, and Rubió. BF has received educational speaking fees from Medice. IT receives funding from the Dutch organisation of research (ZONMW project numbers 80-86200-98-20006, 80-85200-98-20006, 60-63600-98-903) VR has served as a speaker for Rubió and Shire/Takeda in the last 5 years. She has received travel awards from Shire/Takeda for participating in psychiatric meetings. JKB has been in the past 3 years a consultant to / member of advisory board of / and/or speaker for Takeda, Roche, Medice, Angelini, Janssen, and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. He has no other financial or material support, including expert testimony, patents, royalties. BJ, PV, DM, PvE, MR, JV, MB, AAV and MH have nothing further to disclose., (Copyright © 2024. Published by Elsevier B.V.)- Published
- 2024
- Full Text
- View/download PDF