Gut microbiome changes with micronutrient supplementation in children with attention-deficit/hyperactivity disorder: the MADDY study
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Ast HK, Hammer M, Zhang S, Bruton A, Hatsu IE, Leung B, McClure R, Srikanth P, Farris Y, Norby-Adams L, Robinette LM, Arnold LE, Swann JR, Zhu J, Karstens L, Johnstone JM
Journal
Gut microbes
Year
2025
Keywords:
ADHD, children, microbiome, micronutrients
Micronutrients have demonstrated promise in managing inattention and emotional dysregulation in children with attention-deficit/hyperactivity disorder (ADHD). One plausible pathway by which micronutrients improve symptoms is the gut microbiome. This study examines changes in fecal microbial composition and diversity after micronutrient supplementation in children with ADHD (N = 44) and highlights potential mechanisms responsible for the behavioral improvement, as determined by blinded clinician-rated global improvement response to micronutrients. Participants represent a sub-group of the Micronutrients for ADHD in Youth (MADDY) study, a double blind randomized controlled trial in which participants received micronutrients or placebo for 8 weeks, followed by an 8-week open extension. Stool samples collected at baseline, week 8, and week 16 were analyzed using 16S rRNA amplicon sequencing targeting the V4 hypervariable region. Pairwise compositional analyses investigated changes in fecal microbial composition between micronutrients versus placebo and responders versus non-responders. A significant change in microbial evenness, as measured by alpha diversity, and beta-diversity, as measured by Bray-Curtis, was observed following micronutrients supplementation. The phylum Actinobacteriota decreased in the micronutrients group compared to placebo. Two butyrate-producing bacterial families: Rikenellaceae and Oscillospiraceae, exhibited a significant increase in change following micronutrients between responders versus non-responders. These findings suggest that micronutrients modulated the composition of the fecal microbiota and identified specific bacterial changes associated with micronutrient responders.
Experiment 1
Subjects
- Location of subjects
- Canada
- United States of America
- 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
- Micronutrient Micronutrient,micronutrient
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Placebo
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Micronutrient
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Children with ADHD who received micronutrient supplementation after the 8 week randomized controlled trial(RCT) period
- Group 0 sample size Number of subjects in the control (unexposed) group
- 11
- Group 1 sample size Number of subjects in the case (exposed) group
- 33
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V4
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
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)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
Alpha Diversity
- Pielou Quantifies how equal the community is numerically
- increased
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- increased
Signature 2
Source: Figure 3B
Description: Changes in relative abundance in gut microbial composition following micronutrient supplementation compared to placebo
Abundance in Group 1: decreased abundance in Micronutrient
| NCBI | Quality Control | Links |
|---|---|---|
| Actinomycetota | ||
| Bifidobacteriaceae | ||
| Bifidobacterium | ||
| Faecalibacterium |
Experiment 2
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Placebo before intervention
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Placebo after intervention
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- These are participants who received the placebo during the first study phase (baseline to week 8) and the micronutrients during the second phase (week 8 to week 16)
- Group 1 sample size Number of subjects in the case (exposed) group
- 11
Lab analysis
Statistical Analysis
Experiment 3
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Micronutrient before intervention
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Micronutrient after Intervention
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Children who received a placebo first, followed by micronutrients (week 8 to week 16).
- Group 0 sample size Number of subjects in the control (unexposed) group
- 33
Lab analysis
Statistical Analysis
Alpha Diversity
- Pielou Quantifies how equal the community is numerically
- increased
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- increased
Signature 1
Source: Table 2
Description: Significant within-group changes in bacterial abundance with micronutrients from baseline to week 8.
Abundance in Group 1: increased abundance in Micronutrient after Intervention
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroidaceae | ||
| Bacteroides | ||
| Bacteroidota | ||
| Rikenellaceae |
Revision editor(s): Mautin
Signature 2
Source: Table 2
Description: Significant within-group changes in bacterial abundance with micronutrients from baseline to week 8.
Abundance in Group 1: decreased abundance in Micronutrient after Intervention
| NCBI | Quality Control | Links |
|---|---|---|
| Actinomycetota | ||
| Agathobacter | ||
| Bifidobacteriaceae | ||
| Bifidobacterium | ||
| Blautia | ||
| Lachnospiraceae | ||
| Subdoligranulum | ||
| Bacillota |
Revision editor(s): Mautin
Experiment 4
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Treatment outcome measurement Treatment outcome measurement,treatment outcome measurement
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Non-responders
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Responders
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Participants who showed improvement after micronutrients.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 20
- Group 1 sample size Number of subjects in the case (exposed) group
- 24
Lab analysis
Statistical Analysis
Alpha Diversity
- Pielou Quantifies how equal the community is numerically
- unchanged
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- unchanged
Signature 1
Source: Figure 6
Description: Change in Relative Abundance During Micronutrient Intervention
Abundance in Group 1: increased abundance in Responders
| NCBI | Quality Control | Links |
|---|---|---|
| Rikenellaceae | ||
| Oscillospiraceae |
Revision editor(s): Mautin
Experiment 5
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Responders before treatment
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Responders after treatment
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Participants who exhibited a clinical response to micronutrients.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 24
Lab analysis
Statistical Analysis
Alpha Diversity
- Pielou Quantifies how equal the community is numerically
- increased
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- increased
Signature 1
Source: Table 4
Description: Significant bacterial abundance within-group change following micronutrient treatment by response group.
Abundance in Group 1: increased abundance in Responders after treatment
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroidaceae | ||
| Bacteroides | ||
| Bacteroidota | ||
| Rikenellaceae | ||
| Oscillospiraceae |
Revision editor(s): Mautin
Signature 2
Source: Table 4
Description: Significant bacterial abundance within-group change following micronutrient treatment by response group.
Abundance in Group 1: decreased abundance in Responders after treatment
| NCBI | Quality Control | Links |
|---|---|---|
| Agathobacter | ||
| Bifidobacteriaceae | ||
| Bifidobacterium | ||
| Blautia | ||
| Actinomycetota |
Revision editor(s): Mautin
Experiment 6
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Non-Responders before treatment
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Non-Responders after treatment
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Participants who did not exhibited a clinical response to micronutrients.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 20
- Group 1 sample size Number of subjects in the case (exposed) group
- 20
Lab analysis
Statistical Analysis
Alpha Diversity
- Inverse Simpson Modification of Simpsons index D as 1/D to obtain high values in datasets of high diversity and vice versa
- increased
Signature 2
Source: Table 4
Description: Significant bacterial abundance within-group change following micronutrient treatment by response group.
Abundance in Group 1: decreased abundance in Non-Responders after treatment
| NCBI | Quality Control | Links |
|---|---|---|
| Agathobacter | ||
| Bifidobacteriaceae | ||
| Bifidobacterium | ||
| Lachnospiraceae | ||
| Actinomycetota |
Revision editor(s): Mautin
Experiment 7
Differences from previous experiment shown
Subjects
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Micronutrient Micronutrient,micronutrient
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Placebo first before micronutrient
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Placebo first after micronutrient
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- These are participants who received the placebo before receiving micronutrients (Week 8 to week 16)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 11
- Group 1 sample size Number of subjects in the case (exposed) group
- 11
Lab analysis
Statistical Analysis
Signature 1
Source: Table S6
Description: Significant Bacterial Taxa Abundance Within Group Change Following Micronutrients Only.
Abundance in Group 1: increased abundance in Placebo first after micronutrient
| NCBI | Quality Control | Links |
|---|---|---|
| Pseudomonadota |
Revision editor(s): Mautin
Signature 2
Source: Table S6
Description: Significant Bacterial Taxa Abundance Within Group Change Following Micronutrients Only.
Abundance in Group 1: decreased abundance in Placebo first after micronutrient
| NCBI | Quality Control | Links |
|---|---|---|
| Agathobacter |
Revision editor(s): Mautin
Experiment 8
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Micronutrients Only before micronutrients
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Micronutrients Only after micronutrients
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- These are participants who received only micronutrients from baseline to week 8 .
- Group 0 sample size Number of subjects in the control (unexposed) group
- 33
- Group 1 sample size Number of subjects in the case (exposed) group
- 33
Lab analysis
Statistical Analysis
Signature 1
Source: Table S6
Description: Significant Bacterial Taxa Abundance Within Group Change Following Micronutrients Only.
Abundance in Group 1: increased abundance in Micronutrients Only after micronutrients
| NCBI | Quality Control | Links |
|---|---|---|
| Bacteroides | ||
| Bacteroidaceae | ||
| Rikenellaceae | ||
| Bacteroidota |
Revision editor(s): Mautin
Signature 2
Source: Table S6
Description: Significant Bacterial Taxa Abundance Within Group Change Following Micronutrients Only.
Abundance in Group 1: decreased abundance in Micronutrients Only after micronutrients
| NCBI | Quality Control | Links |
|---|---|---|
| Agathobacter | ||
| Bifidobacteriaceae | ||
| Bifidobacterium | ||
| Blautia | ||
| Lachnospiraceae | ||
| Subdoligranulum | ||
| Actinomycetota |
Revision editor(s): Mautin
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