Gut microbiota and plasma cytokine levels in patients with attention-deficit/hyperactivity disorder

Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a common childhood mental disorder with undetermined pathophysiological mechanisms. The gut microbiota and immunological dysfunction may influence brain functions and social behaviours. In the current study, we aimed to explore the correlation of gut microbiome imbalance and inflammation in the pathophysiology of ADHD. Forty-one children with ADHD and thirty-nine healthy-control (HC) individuals were recruited. Faecal samples from all participants were collected and submitted for 16 S rRNA V3–V4 amplicon microbiome sequencing analysis. The plasma levels of 10 cytokines, including TNF-α, IL-6, IL-1β, IL-2, IL-10, IL-13, IL-17A, IFN-α2, IFN-γ, and MCP-1, were determined using a custom-made sandwich enzyme-linked immunosorbent assay (ELISA) developed by Luminex Flowmetrix. There was no significant difference between the ADHD and HC groups in species diversity in the faeces, as determined with α-diversity and β-diversity analysis. In the ADHD group, three differentially abundant taxonomic clades at the genus level were observed, namely Agathobacter, Anaerostipes, and Lachnospiraceae. Top differentially abundant bacteria and representative biological pathways were identified in children with ADHD using linear discriminant analysis (LDA) effect size (LEfSe), and the phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analysis, respectively. The plasma levels of TNF-α were significantly lower in children with ADHD than in HCs. Within the ADHD group, the levels of TNF-α were negatively correlated with ADHD symptoms and diversity of the gut microbiome. Our study provides new insights into the association between gut microbiome dysbiosis and immune dysregulation, which may contribute to the pathophysiology of ADHD.

Cytokine Levels and Neuropsychological Function among Patients with Attention-Deficit/Hyperactivity Disorder and Atopic Diseases

“…Meanwhile, cytokines TNF-α, IFN-γ, and IL-17 were negatively correlated with ADHD symptoms. Previous studies have also shown that TNF-αplasma levels in the ADHD group were significantly lower than those in the control group [ 33 , 34 ]. However, another study demonstrated that TNF-α did not differ significantly between the ADHD group and the control group, nor was there significant correlation with parent-assessed ADHD symptoms [ 35 ].…”

Gut Microbiota Profiles in Children and Adolescents with Psychiatric Disorders

“…Alpha diversity of intestinal microbiota between the ADHD and control groups did not differ significantly in five studies [ 17 , 77 , 78 , 79 , 80 ]. One study reported decreased alpha diversity in ADHD patients, and moreover, this result negatively correlated with hyperactivity symptoms [ 81 ].…”

“…Decreased levels of Faecalibacterium [ 77 , 78 ], Haemophilus [ 79 ], Prevotella , Parabacteroides [ 81 ], Lachnoclostridium, Sutterella , Dialister [ 78 ], and Veillonella [ 77 ] were reported in the ADHD group. On the other hand, elevated amounts of Agathobacter, Anaerostipes , Lachnospiraceae_UCG_010 [ 80 ], Neisseria [ 81 ], Fusobacterium [ 6 ], Ruminococcaceae_UCG_004 [ 79 ], Enterococcus , and Odoribacter [ 77 ] were observed. The genus Ruminococcaceae_UCG_004 was associated with inattention scores on the Conners Adult ADHD Rating Scales (CAARS) and Conners Teacher Rating Scale (CTRS) [ 79 ].…”

“…Wan and colleagues (2020) hypothesized that Faecalibacterium dysregulation may cause changes in inflammatory cytokine levels, and therefore participate in ADHD pathogenesis [ 77 ]. Lower plasma TNFα levels in ADHD patients vs. healthy controls were found in one study [ 80 ], but no association between other cytokine levels and ADHD were observed [ 80 ]. An earlier published study described a significant increase in Eggerthella , Alistipes , Odoribacter , Parabacteroides , and Bifidobacterium , while the latter was associated with significantly enhanced predicted biosynthesis potential of a dopamine precursor (phenylalanine) in the gut microbiome of ADHD patients, which was linked to altered reward anticipation responses in the brain, a neural hallmark of ADHD [ 17 ].…”

Association between Gut Microbiota and Emotional-Behavioral Symptoms in Children with Attention-Deficit/Hyperactivity Disorder

“…Research has suggested that the level of SCFAs was relevant to inflammatory bowel conditions with comorbid depression and anxiety [ 60 , 61 ]. The abundance of Agathobacter has also been determined to be associated with ADHD and sleep problems in a population with autism spectrum disorder [ 62 , 63 ]. There is a paucity of information on the role of Agathobacter in the pathophysiology of depression.…”