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

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.

Two-sample Mendelian randomization analysis investigates causal associations between gut microbiota and attention deficit hyperactivity disorder

“…This technology not only allows for more precise identification of the species composition in a sample, but also provides insights into functional composition and metabolic pathways ( Gu et al, 2019 ). Li et al (2022) utilized this approach to sequence 207 human fecal samples and analyzed the gut microbial profiles of ADHD patients with different phenotypes. All the approaches exemplified above will help us to have a deeper understanding of the role of gut microbiota in ADHD.…”

Alteration of the gut microbiome and correlated metabolism in a rat model of long-term depression

“…Alistipes, primarily isolated from medical clinical samples, is a relatively new genus that is highly relevant in dysbiosis and disease, including mental signs of depression ( Parker et al., 2020 ). A recent study revealed gut microbiota characteristics of ADHD and found that low levels of Bacteroides ovatus were associated with host cognitive impairment ( Li et al., 2022 ). Bacteroides ovatus colonization has also been reported to influence the abundance of intestinal short-chain fatty acids and neurotransmitters ( Horvath et al., 2022 ).…”

Metagenomic Analysis Reveals Difference of Gut Microbiota in ADHD

“…Only two studies used shotgun metagenomics sequencing which could provide additional information of gut microbiota species to better understand its role in ADHD (Y. Li et al, 2022;Wang et al, 2022). We performed meta-analyses for these results, and found outcomes varied greatly between studies (Wang et al, 2022).…”

“…The latest 10 researches investigated the possible correlation between the gut microbiota and ADHD, but researchers still have not reached consistent conclusions (Aarts et al, 2017; Jiang et al, 2018; Y. Li et al, 2022; Prehn-Kristensen et al, 2018; Richarte et al, 2021; Szopinska-Tokov et al, 2020; Wan et al, 2020; Wang et al, 2020, 2022; Zhou et al, 2021).…”