Abstract:Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. Given the growing evidence of gut microbiota being involved in psychiatric (including neurodevelopmental) disorders, we aimed to identify differences in gut microbiota composition between participants with ADHD and controls and to investigate the role of the microbiota in inattention and hyperactivity/impulsivity. Fecal samples were collected from 107 participants (NADHD=42; Ncontrols=50; NsubthreholdADHD=15; range age: 13… Show more
“…The metagenomic data here may not directly compare with those results from 16S rRNA sequencing analysis [18][19][20][21][22]. Nevertheless, our findings demonstrated gut dysbiosis in patients with ADHD compared with HCs, which was consistent with previous studies.…”
Section: Discussionsupporting
confidence: 64%
“…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.…”
Section: Discussionmentioning
confidence: 76%
“…Studies based on 16S rRNA sequencing have preliminarily distinguished different gut microbiota between ADHD patients and healthy controls (HCs) from several small size cohorts [18][19][20][21][22]. However, no studies have been carried out to compare bacterial variation between patients with different ADHD symptomatic profiles and HCs.…”
BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a highly heterogeneous psychiatric disorder that can be divided into inattentive (I-ADHD), hyperactive-impulsive (HI-ADHD), and combined (C-ADHD) subtypes. Different early life events and environmental factors correlated with the gut microbiota community have been implicated in the development of ADHD. However, whether different ADHD symptomatic presentations are associated with distinct microbiota composition and function still unknown. Therefore, we carried out metagenomic analysis from 207 subjects to characterize the gut microbial profiles in ADHD and subgroup patients.ResultsThe current study revealed that the gut microbiota composition (beta diversity) can be effectively distinguished between C-ADHD patients and HCs, but not I-ADHD patients and HCs, nor general ADHD patients and HCs. Features include underrepresentation of 8 species belonging to the genus Bacteroides and enrichment of 5 species of Bifidobacterium and Prevotella in general ADHD patients (all p < 0.05). Eight of the above species became progressively reduced (ovatus, thetaiotaomicron, intestinalis, cellulosilyticus, and fluxus belonging to the genus Bacteroides) or enriched (Prevotella_copri, Prevotella_buccae and Bifidobacterium_breve) from healthy controls (HCs) to I-ADHD and C-ADHD patients. Predicted metabolic functions from these distinguished gut microbial markers described a certain compensatory host metabolism in ADHD and subgroup patients. Particularly, pyridoxal 5'-phosphate (a dominant vitamin B6 active type) biosynthesis pathways were significantly reduced in C-ADHD patients, because serum vitamin B6 deficiency in ADHD patients was found previously. Of note, we identified diverse virulence factor and antibiotic resistance from the gut microbiota of ADHD patients. The abundance of antibiotic resistance ontology ANT(9)-Ia positively correlated with the abundance of Prevotella_amnii, which was enriched in ADHD patients. Moreover, species-based bacterial markers were used to construct classifiers and achieved a higher AUC of 0.87 in C-ADHD vs. HC than that in ADHD vs. HC (AUC = 0.84).ConclusionsThese findings uncover alterations in microbial composition in subgroup patients and provide potential biomarkers for diagnosis different symptomatic presentations for ADHD.Trial registration: ClinicalTrials.gov, NCT03447223. Registered 27 February 2018, https://clinicaltrials.gov/ct2/show/NCT03447223?term=03447223&draw=2&rank=1
“…The metagenomic data here may not directly compare with those results from 16S rRNA sequencing analysis [18][19][20][21][22]. Nevertheless, our findings demonstrated gut dysbiosis in patients with ADHD compared with HCs, which was consistent with previous studies.…”
Section: Discussionsupporting
confidence: 64%
“…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.…”
Section: Discussionmentioning
confidence: 76%
“…Studies based on 16S rRNA sequencing have preliminarily distinguished different gut microbiota between ADHD patients and healthy controls (HCs) from several small size cohorts [18][19][20][21][22]. However, no studies have been carried out to compare bacterial variation between patients with different ADHD symptomatic profiles and HCs.…”
BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a highly heterogeneous psychiatric disorder that can be divided into inattentive (I-ADHD), hyperactive-impulsive (HI-ADHD), and combined (C-ADHD) subtypes. Different early life events and environmental factors correlated with the gut microbiota community have been implicated in the development of ADHD. However, whether different ADHD symptomatic presentations are associated with distinct microbiota composition and function still unknown. Therefore, we carried out metagenomic analysis from 207 subjects to characterize the gut microbial profiles in ADHD and subgroup patients.ResultsThe current study revealed that the gut microbiota composition (beta diversity) can be effectively distinguished between C-ADHD patients and HCs, but not I-ADHD patients and HCs, nor general ADHD patients and HCs. Features include underrepresentation of 8 species belonging to the genus Bacteroides and enrichment of 5 species of Bifidobacterium and Prevotella in general ADHD patients (all p < 0.05). Eight of the above species became progressively reduced (ovatus, thetaiotaomicron, intestinalis, cellulosilyticus, and fluxus belonging to the genus Bacteroides) or enriched (Prevotella_copri, Prevotella_buccae and Bifidobacterium_breve) from healthy controls (HCs) to I-ADHD and C-ADHD patients. Predicted metabolic functions from these distinguished gut microbial markers described a certain compensatory host metabolism in ADHD and subgroup patients. Particularly, pyridoxal 5'-phosphate (a dominant vitamin B6 active type) biosynthesis pathways were significantly reduced in C-ADHD patients, because serum vitamin B6 deficiency in ADHD patients was found previously. Of note, we identified diverse virulence factor and antibiotic resistance from the gut microbiota of ADHD patients. The abundance of antibiotic resistance ontology ANT(9)-Ia positively correlated with the abundance of Prevotella_amnii, which was enriched in ADHD patients. Moreover, species-based bacterial markers were used to construct classifiers and achieved a higher AUC of 0.87 in C-ADHD vs. HC than that in ADHD vs. HC (AUC = 0.84).ConclusionsThese findings uncover alterations in microbial composition in subgroup patients and provide potential biomarkers for diagnosis different symptomatic presentations for ADHD.Trial registration: ClinicalTrials.gov, NCT03447223. Registered 27 February 2018, https://clinicaltrials.gov/ct2/show/NCT03447223?term=03447223&draw=2&rank=1
“…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 ].…”
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that occurs in children characterized by inattention and hyperactivity. Prenatal alcohol exposure (PAE) can disrupt fetal neuronal development and cause an ADHD-like hyperactive behavior in the offspring. In this study, we hypothesized that metabolic disturbance would involve in ADHD neuropathology and aimed to investigate the changes in metabolite profile in PAE-induced ADHD-like model and the effects of HX106, a nutraceutical, on ADHD-like pathophysiology and metabolite changes. To this end, we administered HX106 to the mouse offspring affected by PAE (OPAE) and assessed the hyperactivity using the open field test. We observed that HX106-treated OPAE showed less hyperactive behavior than vehicle-treated OPAE. The effects of HX106 were found to be related to the regulation of dopamine transporter and D2 dopamine receptor expression. Furthermore, using gas chromatography time-of-flight mass spectrometry-based metabolomics, we explored the metabolite changes among the experimental groups. The metabolite profile, particularly related with the amino acids, linoleic acid and amino sugar pathways, was altered by PAE and reversed by HX106 treatment partially similar to that observed in the control group. Overall, this study suggest that metabolite alteration would be involved in ADHD pathology and that HX106 can be an efficient supplement to overcome ADHD by regulating dopamine signaling-related protein expression and metabolite changes.
“…Sequencing was performed on the Illumina HiSeq PE300 platform by GATC Biotech AG (Konstanz, Germany). The sequences were processed using NG-Tax (57) analysis pipeline as described previously (58). This resulted in an Operational Taxonomical Unit (OTU) table containing 844 OTUs.…”
Research on the gut-brain axis has accelerated substantially over the course of the last years. Many reviews have outlined the important implications of understanding the relation of the gut microbiota with human brain function and behavior. One substantial drawback in integrating gut microbiome and brain data is the lack of integrative multivariate approaches that enable capturing variance in both modalities simultaneously. To address this issue, we applied a linked independent component analysis (LICA) to microbiota and brain connectivity data. We analyzed data from 58 healthy females (mean age=21.5 years). Magnetic Resonance Imaging data were acquired using resting state functional imaging data. The assessment of gut microbial composition from feces was based on sequencing of the V4 16S rRNA gene region. We used the LICA model to simultaneously factorize the subjects' large-scale brain networks and microbiome relative abundance data into 10 independent components of spatial and abundance variation. LICA decomposition resulted in four components with non-marginal contribution of the microbiota data. The default mode network featured strongly in three components, whereas the two-lateralized fronto-parietal attention networks contributed to one component. The executive-control (with the default mode) network was associated to another component. We found the abundance of Prevotella genus was associated to the strength of expression of all networks, whereas Bifidobacterium was associated with the default mode and frontoparietal-attention networks. We provide the first exploratory evidence for multivariate associative patterns between the gut microbiota and brain network connectivity in healthy humans, taking into account the complexity of both systems.
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