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It has been widely hypothesized that both diet and the microbiome play a role in the regulation of attention-deficit/hyperactivity disorder (ADHD) behaviour. However, there has been very limited scientific investigation into the potential biological connection. We performed a 10-week pilot study investigating the effects of a broad spectrum micronutrient administration on faecal microbiome content, using 16S rRNA gene sequencing. The study consisted of 17 children (seven in the placebo and ten in the treatment group) between the ages of seven and 12 years, who were diagnosed with ADHD. We found that micronutrient treatment did not drive large-scale changes in composition or structure of the microbiome. However, observed OTUs significantly increased in the treatment group, and showed no mean change in the placebo group. The differential abundance and relative frequency of Actinobacteria significantly decreased post- micronutrient treatment, and this was largely attributed to species from the genus Bifidobacterium . This was compensated by an increase in the relative frequency of species from the genus Collinsella . Further research is required to establish the role that Bifidobacterium contribute towards neuropsychiatric disorders; however, these findings suggest that micronutrient administration could be used as a safe, therapeutic method to modulate Bifidobacterium abundance, which could have potential implications for modulating and regulating ADHD behaviour. Our pilot study provides an initial observation into this area of research, and highlights an interesting avenue for further investigation in a larger cohort. Furthermore, these novel results provide a basis for future research on the biological connection between ADHD, diet and the microbiome.

Background Impulsivity and compulsivity are related to emotional and social maladjustment and often underlie psychiatric disorders. Recently, alterations in microbiota composition have been shown to have implications for brain development and social behavior via the microbiota–gut–brain axis. However, the exact mechanisms are not fully identified. Recent evidence suggests the modulatory effect of synbiotics on gut microbiota and the contribution of these agents in ameliorating symptoms of many psychiatric diseases. To date, no randomized controlled trial has been performed to establish the feasibility and efficacy of this intervention targeting the reduction of impulsivity and compulsivity. We hypothesize that supplementation with synbiotics may be an effective treatment in adults with high levels of impulsivity and/or compulsivity. Methods/design This is a prospective, multicenter, double-blind, randomized controlled trial with two arms: treatment with a synbiotic formula versus placebo treatment. The primary outcome is the response rate at the end of the placebo-controlled phase (response defined as a Clinical Global Impression–Improvement Scale score of 1 or 2 = very much improved or much improved, plus a reduction in the Affective Reactivity Index total score of at least 30% compared with baseline). A total of 180 participants with highly impulsive behavior and a diagnosis of attention deficit/hyperactivity disorder (ADHD) and/or borderline personality disorder, aged 18–65 years old, will be screened at three study centers. Secondary outcome measures, including changes in general psychopathology, ADHD symptoms, neurocognitive function, somatic parameters, physical activity, nutritional intake, and health-related quality of life, will be explored at assessments before, during, and at the end of the intervention. The effect of the intervention on genetics, microbiota, and several blood biomarkers will also be assessed. Gastrointestinal symptoms and somatic complaints will additionally be explored at 1-week follow-up. Discussion This is the first randomized controlled trial to determine the effects of supplementation with synbiotics on reducing impulsive and compulsive behavior. This clinical trial can contribute to explaining the mechanisms involved in the crosstalk between the intestinal microbiome and the brain. If effects can be established by reducing impulsive and compulsive behavior, new cost-effective treatments might become available to these patients. Trial registration ClinicalTrials.gov, NCT03495375 . Registered on 26 February 2018.

Gut microbiota regulate intestinal function and health. However, mounting evidence indicates that they can also influence the immune and nervous systems and vice versa. This article reviews the bidirectional relationship between the gut microbiota and the brain, termed the microbiota-gut-brain (MGB) axis, and discusses how it contributes to the pathogenesis of certain disorders that may involve brain inflammation. Articles were identified with a search of Medline (starting in 1980) by using the key words anxiety, attention-deficit hypersensitivity disorder (ADHD), autism, cytokines, depression, gut, hypothalamic–pituitary–adrenal (HPA) axis, inflammation, immune system, microbiota, nervous system, neurologic, neurotransmitters, neuroimmune conditions, psychiatric, and stress. Various afferent or efferent pathways are involved in the MGB axis. Antibiotics, environmental and infectious agents, intestinal neurotransmitters/neuromodulators, sensory vagal fibers, cytokines, and essential metabolites all convey information to the central nervous system about the intestinal state. Conversely, the hypothalamic–pituitary–adrenal axis, the central nervous system regulatory areas of satiety, and neuropeptides released from sensory nerve fibers affect the gut microbiota composition directly or through nutrient availability. Such interactions seem to influence the pathogenesis of a number of disorders in which inflammation is implicated, such as mood disorder, autism-spectrum disorders, attention-deficit hypersensitivity disorder, multiple sclerosis, and obesity. Recognition of the relationship between the MGB axis and the neuroimmune systems provides a novel approach for better understanding and management of these disorders. Appropriate preventive measures early in life or corrective measures such as use of psychobiotics, fecal microbiota transplantation, and flavonoids are discussed.

Microorganisms in the human intestine (i.e. the gut microbiome) have an increasingly recognized impact on human health, including brain functioning. Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder associated with abnormalities in dopamine neurotransmission and deficits in reward processing and its underlying neuro-circuitry including the ventral striatum. The microbiome might contribute to ADHD etiology via the gut-brain axis. In this pilot study, we investigated potential differences in the microbiome between ADHD cases and undiagnosed controls, as well as its relation to neural reward processing. We used 16S rRNA marker gene sequencing (16S) to identify bacterial taxa and their predicted gene functions in 19 ADHD and 77 control participants. Using functional magnetic resonance imaging (fMRI), we interrogated the effect of observed microbiome differences in neural reward responses in a subset of 28 participants, independent of diagnosis. For the first time, we describe gut microbial makeup of adolescents and adults diagnosed with ADHD. We found that the relative abundance of several bacterial taxa differed between cases and controls, albeit marginally significant. A nominal increase in the Bifidobacterium genus was observed in ADHD cases. In a hypothesis-driven approach, we found that the observed increase was linked to significantly enhanced 16S-based predicted bacterial gene functionality encoding cyclohexadienyl dehydratase in cases relative to controls. This enzyme is involved in the synthesis of phenylalanine, a precursor of dopamine. Increased relative abundance of this functionality was significantly associated with decreased ventral striatal fMRI responses during reward anticipation, independent of ADHD diagnosis and age. Our results show increases in gut microbiome predicted function of dopamine precursor synthesis between ADHD cases and controls. This increase in microbiome function relates to decreased neural responses to reward anticipation. Decreased neural reward anticipation constitutes one of the hallmarks of ADHD.

ADHD is a psychiatric disorder which is characterized by hyperactivity, impulsivity and attention problems. Due to recent findings of microbial involvement in other psychiatric disorders like autism and depression, a role of the gut microbiota in ADHD pathogenesis is assumed but has not yet been investigated. In this study, the gut microbiota of 14 male ADHD patients (mean age: 11.9 yrs.) and 17 male controls (mean age: 13.1 yrs.) was examined via next generation sequencing of 16S rDNA and analyzed for diversity and biomarkers. We found that the microbial diversity (alpha diversity) was significantly decreased in ADHD patients compared to controls (pShannon = 0.036) and that the composition (beta diversity) differed significantly between patients and controls (pANOSIM = 0.033, pADONIS = 0.006, pbetadisper = 0.002). In detail, the bacterial family Prevotellacae was associated with controls, while patients with ADHD showed elevated levels of Bacteroidaceae, and both Neisseriaceae and Neisseria spec. were found as possible biomarkers for juvenile ADHD. Our results point to a possible link of certain microbiota with ADHD, with Neisseria spec. being a very promising ADHD-associated candidate. This finding provides the basis for a systematic, longitudinal assessment of the role of the gut microbiome in ADHD, yielding promising potential for both prevention and therapeutic intervention.

Background The impact of the gut microbiota on host physiology and behavior has been relatively well established. Whether changes in microbial composition affect brain structure and function is largely elusive, however. This is important as altered brain structure and function have been implicated in various neurodevelopmental disorders, like attention-deficit/hyperactivity disorder (ADHD). We hypothesized that gut microbiota of persons with and without ADHD, when transplanted into mice, would differentially modify brain function and/or structure. We investigated this by colonizing young, male, germ-free C57BL/6JOlaHsd mice with microbiota from individuals with and without ADHD. We generated and analyzed microbiome data, assessed brain structure and function by magnetic resonance imaging ( MRI ), and studied mouse behavior in a behavioral test battery. Results Principal coordinate analysis showed a clear separation of fecal microbiota of mice colonized with ADHD and control microbiota. With diffusion tensor imaging, we observed a decreased structural integrity of both white and gray matter regions (i.e., internal capsule, hippocampus) in mice that were colonized with ADHD microbiota. We also found significant correlations between white matter integrity and the differentially expressed microbiota. Mice colonized with ADHD microbiota additionally showed decreased resting-state functional MRI-based connectivity between right motor and right visual cortices. These regions, as well as the hippocampus and internal capsule, have previously been reported to be altered in several neurodevelopmental disorders. Furthermore, we also show that mice colonized with ADHD microbiota were more anxious in the open-field test. Conclusions Taken together, we demonstrate that altered microbial composition could be a driver of altered brain structure and function and concomitant changes in the animals’ behavior. These findings may help to understand the mechanisms through which the gut microbiota contributes to the pathobiology of neurodevelopmental disorders. 7eJBsCA8tMGaQzNiv1LdPB Video abstract.

Attention-deficit/hyperactivity disorder (ADHD), a common neurodevelopmental disorder in children, is associated with alterations in gut microbiota and short-chain fatty acids (SCFAs), which are metabolites influencing the gut-brain axis. Evidence suggests that psychostimulant medications, widely used to manage ADHD symptoms, may also impact gut microbiota composition and SCFA levels. This study explores these potential effects by examining gut microbiota profiles and SCFA concentrations in unmedicated and medicated children with ADHD, compared to healthy controls. Fecal samples from 30 children aged 6–12 years (10 unmedicated ADHD, 10 medicated ADHD, and 10 healthy controls) were analyzed using 16 S rRNA sequencing and targeted metabolomics. Unmedicated ADHD children show distinct gut microbiota profiles, with lower level of Tyzzerella , Prevotellaceae , and Coriobacteriaceae , compared to controls. Notably, propionic acid levels were negatively associated with ADHD symptom severity, suggesting a potential biomarker role. Medicated ADHD children showed lower gut microbial diversity, unique taxa, and lower SCFA levels, compared to unmedicated children with ADHD. These findings suggest that gut microbiota and SCFAs may be linked to ADHD symptomatology, underscoring the importance of gut-brain interactions in ADHD. This study highlights the potential of gut health monitoring as part of future ADHD management strategies.

Patients with attention-deficit hyperactivity disorder (ADHD) reported significantly more constipation and flatulence than healthy controls. An altered gut microbiome can be associated with gastrointestinal symptoms. However, comprehensive information about associated risk of intestinal disorders and ADHD remains limited. A systematic review of the literature was therefore conducted to investigate the association between ADHD and different types of intestinal disorders. A total of 11 studies with 3,851,163 unique individuals, including 175 806 individuals with ADHD and 3 675 357 individuals without ADHD were included. The pooled OR of intestinal disorders for individuals with ADHD was 1.25 (95%CI, 0.75–2.07). A significant positive association was found between ADHD and irritable bowel syndrome (IBS) (OR 1.63 [95% CI 1.45–1.83]). Studies conducted in Eastern Mediterranean Region yielded a summary OR estimate that was higher than summary OR estimates in studies conducted in Region of the Americas, European Region and Western Pacific Region (3.03 [1.53–5.99] vs. 2.20 [1.05–4.63], 1.04 [0.44–2.41], 0.68 [0.25–1.87]), with p value 0.053, indicating a trend towards significance. High heterogeneity was observed. Our study supports association between ADHD and increased risk of IBS. Our study suggests an altered gut microbiome is the potential link that bridges gap between ADHD and intestinal disorder.

Background Evidence indicates the gut microbiome may be altered in ADHD, suggesting that targeting gut bacteria could alleviate symptoms. This study examined the effects of kefir supplementation on ADHD symptoms, sleep, attention, and gut microbiome composition in children diagnosed with ADHD. Methods A six-week, randomised, double-blind, placebo-controlled trial was conducted in UK children aged 8–13 years with ADHD. Participants were assigned either to a daily kefir or placebo drink group. The primary outcome was ADHD symptom severity measured by the Strengths and Weaknesses of ADHD Symptoms and Normal Behaviour (SWAN) scale. Secondary outcomes included gut microbiota composition (analysed using shotgun metagenomic sequencing), gastrointestinal symptoms, sleep (actigraphy, parent/self-report), attention and impulsivity. Results Fifty-three participants (mean age = 10.2 years, SD = 1.7) completed the study. Kefir had no significant overall effect on parent or teacher-rated ADHD symptom severity. A non-significant interaction was observed between baseline symptom severity and group for teacher-rated SWAN scores, with children in the kefir group who had the highest baseline ADHD symptoms showing lower scores at week six ( M  = 2.03, SE = 0.33 vs. 2.86, SE = 0.34), p  = 0.088. Actigraphy revealed the kefir group spent fewer minutes awake during the down period at week six ( M  = 70.10, SE = 0.09) than the placebo group ( M  = 89.72, SE = 0.07), p  = 0.04. However, the kefir group self-reported more sleep problems post-intervention ( M  = 39.81, SE = 0.75 vs. 37.40, SE = 0.65), p  = 0.02. For Go/NoGo RT variance, a non-significant interaction ( p  = 0.052) between baseline and post intervention scores was found. No other significant group differences were observed. Kefir supplementation did not significantly affect gut microbiota alpha or beta diversity. However, relative abundance of several species including bifidobacterium adolescentis, B. infantis , and B. longum and Alistipes sp021204515 and A. timonensi increased significantly in the kefir group. Conclusions Kefir supplementation may support modest improvements in sleep quality, in children with ADHD. These findings contribute to our understanding of the potential role of nutrition in ADHD management and may inform clinical guidance for practitioners working with neurodivergent individuals. Ethics Ethical approval for the study was granted by St Mary’s University Ethics Committee. Trial registration The trial protocol has been prospectively registered with ClinicalTrials.gov: NCT05155696. Registered on 13 December 2021.

Background Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with an increasing prevalence in children. Recent studies have suggested that the gut microbiota may play a significant role in the development of ADHD. However, the specific relationship between changes in intestinal bacteria and related metabolites in children with ADHD remains poorly understood. Results In this study, we illustrated the fecal microbiome, metabolome and lipidome, as well as plasma metabolome using 16S rRNA gene sequencing and LC–MS in 15 pairs of children with ADHD and healthy controls. Our results revealed imbalance of gut microbiota and dysregulation of metabolites in individuals with ADHD. Specifically, children with ADHD exhibited significantly lower abundance of the Actinobacteria phylum, particularly Bifidobacterium , Corynebacterium and Actinomyces , while Veillonella in the Negativicutes class showed significant high level. No children with ADHD were classified under enterotype 1, which was composed solely of healthy children. Integration of multi-omics data suggested that the Bifidobacterium genus, which is positively correlated with various neurotransmitter precursor amino acid metabolites, may contribute to ADHD by downregulating pathways involving dopaminergic, serotonergic and glutamatergic systems. Conclusions These findings highlight the crucial regulatory impact of gut microbiota in the development of ADHD through metabolic pathways, and provide a potential avenue to the diagnosis and intervention of ADHD.