Case-Control Study of the Effects of Gut Microbiota Composition on Neurotransmitter Metabolic Pathways in Children With Attention Deficit Hyperactivity Disorder

Abstract

Background: Attention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric condition that may be related to an imbalance of neural transmitters. The gut microbiota is the largest ecosystem in the human body, and the brain-gut axis theory proposes that the gut microbiome can affect brain function in multiple ways. The purpose of this study was to explore the gut microbiota in children with ADHD and assess the possible role of the gut microbiota in disease pathogenesis to open new avenues for ADHD treatment.Methods: A case-control design was used. We enrolled 17 children aged 6-12 years with ADHD who were treated in the Pediatric Outpatient Department of the First Medical Center of the Chinese PLA General Hospital from January to June, 2019. Seventeen children aged 6-12 years were selected as the healthy control (HC) group. Fecal samples of cases and controls were analyzed by shotgun metagenomics sequencing. Alpha diversity and the differences in the relative abundances of bacteria were compared between the two groups. Functional annotations were performed for the microbiota genes and metabolic pathways were analyzed using the Kyoto Encyclopedia of Genes and Genomes (KEGG). Results:There was no significant difference in the alpha diversity of gut microbiota between the ADHD and HC groups. Compared with HCs, Faecalibacterium and Veillonellaceae were significantly reduced in children with ADHD (P < 0.05), Odoribacter and Enterococcus were significantly increased [linear discriminant analysis (LDA) > 2]. At the species level, Faecalibacterium prausnitzii, Lachnospiraceae bacterium, and Ruminococcus gnavus were significantly reduced in the ADHD group (P < 0.05), while Bacteroides caccae, Odoribacter splanchnicus, Paraprevotella xylaniphila, and Veillonella parvula were increased (P < 0.05). Metabolic pathway analysis revealed significant between-group differences in the metabolic pathways of neurotransmitters (e.g., serotonin and dopamine) (P < 0.05). Frontiers in Neuroscience | www.frontiersin.org 1 February 2020 | Volume 14 | Article 127 Wan et al. Gut Microbiota Role in ADHDConclusion: Composition differences of gut microbiota in subjects with ADHD may contribute to brain-gut axis alterations and affect neurotransmitter levels, which could contribute to ADHD symptoms.

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

“…Notably, the reported distinct bacterial taxa between ADHD patients and HCs were highly inconsistent in previous studies [18][19][20][21][22][23]. The disturbed bacterial taxa in one cohort may never be replicated or may be opposite in abundance in another cohort.…”

“…We found a significantly lower gene number in ADHD or C-ADHD patients than in HCs, though the gut microbiota richness, namely, alpha diversity, was similar between any two groups. There were also no significant differences in alpha diversity between ADHD patients and HCs in the Dutch [18] and Chinese (Zhejiang and Beijing) cohorts [19,23]. However, two other cohorts from Germany [20] and China (Taiwan) [21], showed reduced or increased alpha diversity in ADHD patients, respectively.…”

GC-TOF-MS-Based Metabolomic Analysis and Evaluation of the Effects of HX106, a Nutraceutical, on ADHD-Like Symptoms in Prenatal Alcohol Exposed Mice

“…Recently, there are some efforts to control neurological disorders by applying the gut-brain axis theory, a bidirectional communication between the brain and gastrointestinal tract [ 50 , 51 ]. In cases of ADHD, there is evidence demonstrating that gut microbiota affects brain neurodevelopment [ 52 , 53 , 54 , 55 ]. For instance, Szopinska-Tokov et al suggested that inattentive behavior that appeared in ADHD patients is associated with a specific bacterium [ 53 ].…”

What Does Immunology Have to Do With Normal Brain Development and the Pathophysiology Underlying Tourette Syndrome and Related Neuropsychiatric Disorders?

“…Among these, the decreased abundance in Faecalibacterium spp. yielded also a negative correlation with ADHD severity scores (215,216). This genus is associated with anti-inflammatory skewing of immune responses and its decreased abundance is observed in allergies.…”

“…Next generation "shotgun" (metagenomic) sequencing has been applied to a small study of ADHD youth (216). Interestingly, pathway analyses of gene functional annotations revealed abnormalities of metabolic pathways associated with dopaminergic and serotonergic systems, consistent with their hypofunctionality.…”