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

Abstract

Previous studies have explored the role of the microbiome in attention-deficit/hyperactivity disorder (ADHD). However, whether the microbiome is correlated with emotional–behavioral disturbances, the most common comorbid symptom of ADHD, remains unclear. We established a cross-sectional study in which 6- to 18-year-old children with ADHD who were receiving no medication and a healthy control group of children without ADHD were recruited to analyze their microbiome composition. Microbiota of fecal samples were collected and analyzed using a 16s rRNA gene sequencing approach. In comparison with the healthy control group, the gut microbiota in children with ADHD exhibited significantly lower beta diversity. The abundance of the phylum Proteobacteria and the genera Agathobacter, Phascolarctobacterium, Prevotella_2, Acidaminococcus, Roseburia, and Ruminococcus gnavus group was increased in the ADHD group compared with the healthy group. Linear discriminant effect size (LEfSe) analysis was used to highlight specific bacteria phylotypes that were differentially altered between the ADHD and control groups. A regression analysis was performed to investigate the association between microbiota and emotional–behavioral symptoms in children with ADHD. A significant association was noted between withdrawal and depression symptoms and Agathobacter (p = 0.044), and between rule-breaking behavior and the Ruminococcus gnavus group (p = 0.046) after adjusting for sex, age, and the ADHD core symptoms score. This study advances the knowledge of how gut microbiota composition may contribute to emotional–behavioral symptoms in children with ADHD. The detailed mechanisms underlying the role of the gut microbiota in ADHD pathophysiology still require further investigation.

Inflammation and emotional regulation: a narrative review of evidence and mechanisms in emotional dysregulation disorders

“…Interestingly, a recent cross-sectional study investigated the bacterial strains in the gut microbiome of 54 children affected by ADHD compared to 22 HC and found that the concentrations of the bacterial strains were positively associated with emotional-behavioural symptoms which could result from (or express) ED. (334). In particular, Rhuminococcus was positively correlated with externalizing symptoms (i.e., rule-breaking behaviour) and Agathobacter with internalizing symptoms (i.e., depressive symptoms and withdrawal).…”

“…Like other neuropsychiatric illnesses, ADHD has high comorbidity with gastrointestinal disturbances, such as constipation and abdominal pain (331,332), and diseases, such as ulcerative colitis (333). Some works have also reported discrepancies between ADHD and HC in the microbiome variability (334)(335)(336), which could be associated with distinct proinflammatory profiles and ADHD symptoms (337,338), although results are still inconclusive (339).…”

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

“…Consistent with previous studies, we found that the genus Roseburia and genus Desulfovibrio were associated with ADHD. Lee et al (2022) conducted a cross-sectional study that compared the composition of the gut microbiome in 54 drug-naive children with ADHD and 22 healthy controls, and found that the abundance of the phylum Proteobacteria and the genera Roseburia , Agathobacter , Phascolarctobacterium , Prevotella_2 , Acidaminococcus , and the Ruminococcus gnavus group were increased in the ADHD group compared to the healthy controls. Our study confirms that the increase in genus Roseburia abundance is caused by ADHD, but the underlying mechanism remains to be further investigated.…”

An overview on neurobiology and therapeutics of attention-deficit/hyperactivity disorder

“…Regarding the general composition of the microbiota, while some individual studies have found differences in patients with ADHD in diversity indices (alpha and beta) [ 167 , 168 ], the overall evidence and meta-analyses point to high heterogeneity across studies and do not support a consistent association of diversity indices with ADHD [ 160 , 166 ]. In general, the studies evaluating the microbiota effects on ADHD are limited, and contradictory/inconsistent findings have been reported, likely due to methodological differences and small sample sizes [ 157 ].…”