Investigating the Gut Microbiota Composition of Individuals with Attention-Deficit/Hyperactivity Disorder and Association with Symptoms

Szopinska-Tokov, Joanna; Dam, Sarita; Naaijen, Jilly; Konstanti, Prokopis; Rommelse, Nanda; Belzer, Clara; Buitelaar, Jan K.; Franke, Barbara; Aarts, Esther; Vásquez, Alejandro Arias

doi:10.3390/microorganisms8030406

Cited by 65 publications

(77 citation statements)

References 67 publications

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“…First, a genus was filtered based on 10% prevalence cutoff. Second, a sample with less than 10% of genera was removed (see 31 ). To avoid bias in assessing the effects of the intervention, filtering was done on the pre-intervention session.…”

Section: Data Analyses Bioinformaticsmentioning

confidence: 99%

Probiotics-induced changes in gut microbial composition and its effects on cognitive performance after stress

Bloemendaal

Belzer

Boverhoff

et al. 2020

Preprint

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Stress negatively affects cognitive performance. Probiotics remediate somatic and behavioral stress responses, hypothetically by acting on the gut microbiota. Here, we assessed gut microbial alterations after 28-days supplementation of multi-strain probiotics (EcologicBarrier consisting of Lactobacilli, Lactococci and Bifidobacteria in healthy, female subjects (probiotics group n=27, placebo group n=29). In an identical pre- and post-session, subjects performed a working memory task before and after an acute stress intervention. One-month supplementation of probiotics changed the gut microbial community (within probiotics group Pweighted unifrac=0.008). This change was driven by a nominal increase in eight genera in the probiotics group relative to the placebo group: Butyricimonas, Parabacteroides, Alistipes, Christensenellaceae_R-7_group, Family_XIII_AD3011_group, Ruminococcaceae_UCG-003, Ruminococcaceae_UCG-005 and Ruminococcaceae_UCG-010. Of these, the probiotics-induced change in genus Ruminococcaceae_UCG-003 was significantly associated with probiotics’ effect on stress-induced working memory changes (rspearman(27) = 0.565; pFDR = 0.014) in the probiotics group only and independent of potential confounders (i.e., age, BMI, and baseline dietary fibre intake). That is, subjects with a higher increase in Ruminococcaceae_UCG-003 abundance after probiotics were also more protected from negative effects of stress on working memory after probiotic supplementation. The bacterial taxa showing an increase in relative abundance in the probiotics group are plant fibre degrading bacteria and produce short-chain fatty acids that are known for their beneficial effect on gut and brain health, e.g. maintaining intestinal- and blood-brain-barrier integrity. This study shows that gut microbial alterations, modulated through probiotics use, are related to improved cognitive performance in acute stress circumstances.

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Section: Data Analyses Bioinformaticsmentioning

confidence: 99%

Probiotics-induced changes in gut microbial composition and its effects on cognitive performance after stress

Bloemendaal

Belzer

Boverhoff

et al. 2020

Preprint

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“…Our results show that three genera, Anaerostipes, Roseburia (both from the Lachnospiraceae family), and Ruminococcaceae UGC-004 (Family Ruminococcaceae), positively correlated with anxiety levels, while Eubacterium appeared to be negatively correlated to the severity of anxiety and positively with anxiety reduction. Importantly, these genera were also found to be more abundant in persons with ADHD, compared to controls, as part of our ongoing study of ADHD patients from the NeuroIMAGE study [73] (n = 56) and healthy participants (n = 49) [74].…”

Section: Discussionmentioning

confidence: 93%

Gut microbiota from persons with attention-deficit/hyperactivity disorder affects the brain in mice

Tengeler¹,

Dam

Wiesmann³

et al. 2020

Microbiome

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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.

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“…Increased abundance in the Bifidobacterium genus was found in adolescents/adults with ADHD (217) and, although remaining a controversial finding (218), was reversed by micronutrient supplementation in a recent randomized controlled trial (RCT) (219). The largest study that used 16S rRNA amplicon sequencing investigated adolescents/adults with ADHD and identified increased relative abundance of different, potentially interacting, Ruminococcaceae genera, and positive correlation with inattentive symptoms (218). The same group performed an exploratory fecal matter transplantation study of stool specimens from ADHD patients into germ-free mice, generating anxietylike behaviors (220).…”

Section: Association With Specific Gut Microbiota Profilesmentioning

confidence: 98%

“…However, this finding needs to be verified adjusting for dietary habits, as certain diets like the long-term Mediterranean are associated with higher abundance in Faecalibacterium spp. Increased abundance in the Bifidobacterium genus was found in adolescents/adults with ADHD (217) and, although remaining a controversial finding (218), was reversed by micronutrient supplementation in a recent randomized controlled trial (RCT) (219). The largest study that used 16S rRNA amplicon sequencing investigated adolescents/adults with ADHD and identified increased relative abundance of different, potentially interacting, Ruminococcaceae genera, and positive correlation with inattentive symptoms (218).…”

Section: Association With Specific Gut Microbiota Profilesmentioning

confidence: 99%

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

2020

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The goal of this article is to review the past decade's literature and provide a critical commentary on the involvement of immunological mechanisms in normal brain development, as well as its role in the pathophysiology of Tourette syndrome, other Chronic tic disorders (CTD), and related neuropsychiatric disorders including Obsessive-compulsive disorder (OCD) and Attention deficit hyperactivity disorder (ADHD). Methods: We conducted a literature search using the Medline/PubMed and EMBASE electronic databases to locate relevant articles and abstracts published between 2009 and 2020, using a comprehensive list of search terms related to immune mechanisms and the diseases of interest, including both clinical and animal model studies. Results: The cellular and molecular processes that constitute our "immune system" are crucial to normal brain development and the formation and maintenance of neural circuits. It is also increasingly evident that innate and adaptive systemic immune pathways, as well as neuroinflammatory mechanisms, play an important role in the pathobiology of at least a subset of individuals with Tourette syndrome and related neuropsychiatric disorders In the conceptual framework of the holobiont theory, emerging evidence points also to the importance of the "microbiota-gut-brain axis" in the pathobiology of these neurodevelopmental disorders. Conclusions: Neural development is an enormously complex and dynamic process. Immunological pathways are implicated in several early neurodevelopmental processes including the formation and refinement of neural circuits. Hyper-reactivity of systemic immune pathways and neuroinflammation may contribute to the natural fluctuations of the core behavioral features of CTD, OCD, and ADHD. There is still limited knowledge of the efficacy of direct and indirect (i.e., through environmental modifications) immune-modulatory interventions in the treatment of these disorders. Future research also needs to focus on the key molecular pathways through which dysbiosis of different tissue microbiota influence neuroimmune interactions in these disorders, Martino et al. Immunity in TS/CTD, OCD, and ADHD and how microbiota modification could modify their natural history. It is also possible that valid biomarkers will emerge that will guide a more personalized approach to the treatment of these disorders.

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Investigating the Gut Microbiota Composition of Individuals with Attention-Deficit/Hyperactivity Disorder and Association with Symptoms

Cited by 65 publications

References 67 publications

Probiotics-induced changes in gut microbial composition and its effects on cognitive performance after stress

Probiotics-induced changes in gut microbial composition and its effects on cognitive performance after stress

Gut microbiota from persons with attention-deficit/hyperactivity disorder affects the brain in mice

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

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