Gut metagenomics discriminates unique microbial signatures in diverse symptomatic profiles with attention-deficit/hyperactivity disorder

Abstract BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a highly heterogeneous psychiatric disorder that can be divided into inattentive (I-ADHD), hyperactive-impulsive (HI-ADHD), and combined (C-ADHD) subtypes. Different early life events and 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 composition and function still unknown. Therefore, we carried out metagenomic analysis from 207 subjects to characterize the gut microbial profiles in ADHD and subgroup patients.ResultsThe current study revealed that the gut microbiota composition (beta diversity) can be effectively distinguished between C-ADHD patients and HCs, but not I-ADHD patients and HCs, nor general ADHD patients and HCs. Features include underrepresentation of 8 species belonging to the genus Bacteroides and enrichment of 5 species of Bifidobacterium and Prevotella in general ADHD patients (all p < 0.05). Eight of the above species became progressively reduced (ovatus, thetaiotaomicron, intestinalis, cellulosilyticus, and fluxus belonging to the genus Bacteroides) or enriched (Prevotella_copri, Prevotella_buccae and Bifidobacterium_breve) from healthy controls (HCs) to I-ADHD and C-ADHD patients. Predicted metabolic functions from these distinguished gut microbial markers described a certain compensatory host metabolism in ADHD and subgroup patients. Particularly, pyridoxal 5'-phosphate (a dominant vitamin B6 active type) biosynthesis pathways were significantly reduced in C-ADHD patients, because serum vitamin B6 deficiency in ADHD patients was found previously. Of note, we identified diverse virulence factor and antibiotic resistance from the gut microbiota of ADHD patients. The abundance of antibiotic resistance ontology ANT(9)-Ia positively correlated with the abundance of Prevotella_amnii, which was enriched in ADHD patients. Moreover, species-based bacterial markers were used to construct classifiers and achieved a higher AUC of 0.87 in C-ADHD vs. HC than that in ADHD vs. HC (AUC = 0.84).ConclusionsThese findings uncover alterations in microbial composition in subgroup patients and provide potential biomarkers for diagnosis different symptomatic presentations for ADHD.Trial registration: ClinicalTrials.gov, NCT03447223. Registered 27 February 2018, https://clinicaltrials.gov/ct2/show/NCT03447223?term=03447223&draw=2&rank=1