Gut microbiome in ADHD and its relation to neural reward anticipation

Study information

Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

28863139

DOI Digital object identifier for electronic documents.

10.1371/journal.pone.0183509

URI

Authors

Aarts E, Ederveen THA, Naaijen J, Zwiers MP, Boekhorst J, Timmerman HM, Smeekens SP, Netea MG, Buitelaar JK, Franke B, van Hijum SAFT, Arias Vasquez A

Journal

PloS one

Year

2017

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Experiment 1

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Victoria

Subjects

Location of subjects: Netherlands

Host species Species from which microbiome was sampled. Contact us to have more species added.: Homo sapiens

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology: Attention deficit hyperactivity disorder ADD,ADDH,ADHD,ATTENTION DEFICIT DIS,ATTENTION DEFICIT DIS WITH HYPERACTIVITY,Attention Deficit Disorder,attention deficit disorder,Attention Deficit Disorder with Hyperactivity,Attention Deficit Disorders,Attention Deficit Disorders with Hyperactivity,ATTENTION DEFICIT HYPERACTIVITY DIS,attention deficit hyperactivity disorder, inattentive type,attention deficit hyperactivity disorder, inattentive/distractible type,attention deficit hyperactivity disorder, predominantly inattentive type,Attention Deficit Hyperactivity Disorders,Brain Dysfunction, Minimal,Deficit Disorder, Attention,Deficit Disorders, Attention,Disorder, Attention Deficit,Disorders, Attention Deficit,Dysfunction, Minimal Brain,hyperkinetic disorder,Hyperkinetic Syndrome,Minimal Brain Dysfunction,Syndromes, Hyperkinetic,Attention deficit hyperactivity disorder,attention deficit hyperactivity disorder

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Controls

Group 1 name Corresponds to the case (exposed) group for case-control studies: ADHD

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: cases were diagnosed based on DSM-IV symptoms using the Schedule for Affective Disorders and Schizophrenia for School-Age Children

Group 0 sample size Number of subjects in the control (unexposed) group: 77

Group 1 sample size Number of subjects in the case (exposed) group: 19

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V3-V4

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance: Roche454

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).: relative abundances

Statistical test: Mann-Whitney (Wilcoxon)

Significance threshold p-value or FDR threshold used for differential abundance testing (if any): 0.1

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: No

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness: unchanged

Chao1 Abundance-based estimator of species richness: unchanged

Signature 1

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: Fatima Zohra

Revision editor(s): WikiWorks

Source: Figure 3

Description: Differential abundance of microbial taxa for ADHD cases versus healthy controls

Abundance in Group 1: increased abundance in ADHD

NCBI	Quality Control	Links
Actinomycetota
Actinomycetes
Bifidobacteriales
Bifidobacteriaceae
Bifidobacterium
Eggerthella
Bifidobacterium pseudocatenulatum
Bifidobacterium longum subsp. longum
Bifidobacterium adolescentis
Odoribacter
Porphyromonadaceae
Rikenellaceae
Parabacteroides
Alistipes
Phocaeicola vulgatus
Bacteroides ovatus
Bacteroides uniformis
Deltaproteobacteria
Desulfovibrionales