Gut metagenomic characteristics of ADHD reveal low Bacteroides ovatus-associated host cognitive impairment

Gut Microbes. 2022 Jan-Dec;14(1):2125747. doi: 10.1080/19490976.2022.2125747.

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a highly heterogeneous psychiatric disorder that can have three phenotypical presentations: inattentive (I-ADHD), hyperactive-impulsive (HI-ADHD), and combined (C-ADHD). Environmental factors correlated with the gut microbiota community have been implicated in the development of ADHD. However, whether different ADHD symptomatic presentations are associated with distinct microbiota compositions and whether patients could benefit from the correction of aberrant bacterial colonization are still largely unclear. We carried out metagenomic shotgun analysis with 207 human fecal samples to characterize the gut microbial profiles of patients with ADHD grouped according to their phenotypical presentation. Then, we transplanted the candidate low-abundance bacteria identified in patient subgroups into ADHD rats and evaluated ADHD-associated behaviors and neuronal activation in these rats. Patients with C-ADHD had a different gut microbial composition from that of healthy controls (HCs) (p = .02), but not from that of I-ADHD patients. Eight species became progressively attenuated or enriched when comparing the compositions of HCs to those of I-ADHD and C-ADHD; in particular, the abundance of Bacteroides ovatus was depleted in patients with C-ADHD. In turn, Bacteroides ovatus supplementation ameliorated spatial working memory deficits and reversed θ electroencephalogram rhythm alterations in ADHD rats. In addition, Bacteroides ovatus induced enhanced neuronal activation in the hippocampal CA1 subregion. These findings indicate that gut microbial characteristics that are unique to patients with C-ADHD may be masked when considering a more heterogeneous group of patients. We link the gut microbiota to brain function in an ADHD animal model, suggesting the relevance of testing a potential bacteria-based intervention for some aspects of ADHD.

Keywords: ADHD; Bacteroides ovatus; electroencephalogram rhythms; gut microbiota; hippocampus; metagenomic sequencing; microbiota-gut-brain axis; spatial working memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Attention Deficit Disorder with Hyperactivity* / microbiology
  • Bacteroides
  • Cognition
  • Cognitive Dysfunction*
  • Gastrointestinal Microbiome* / physiology
  • Humans
  • Rats

Supplementary concepts

  • Bacteroides ovatus

Grants and funding

This work was supported by the National Natural Science Foundation of China (No. 92057111, 82071538), the Funds for the State Key Program of National Natural Science Foundation of China (No. 81730032), the Natural Science Fund for Distinguished Young Scholars of Shaanxi Province (2019JC-24), the Fundamental Research Funds for the Central Universities of China (xtr022019005), and the Clinical Research Award of the First Affiliated Hospital of Xi’an Jiaotong University (XJTU1AF-CRF-2018-003).