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Gut microbiome changes with micronutrient supplementation in children with attention–deficit/hyperactivity disorder: the MADDY study

Gut microbiome changes with micronutrient supplementation in children with attention–deficit/hyperactivity disorder: the MADDY study
Gut microbiome changes with micronutrient supplementation in children with attention–deficit/hyperactivity disorder: the MADDY study

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.

ADHD, children, microbiome, micronutrients
1949-0976
Ast, Hayleigh K.
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Hammer, Matthew
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Zhang, Shiqi
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Bruton, Alisha
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Hatsu, Irene E.
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Leung, Brenda
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McClure, Ryan
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Srikanth, Priya
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Farris, Yuliya
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Norby-Adams, Lydia
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Robinette, Lisa M.
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Arnold, L. Eugene
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Swann, Jonathan R.
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Zhu, Jiangjiang
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Karstens, Lisa
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Johnstone, Jeanette M.
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Ast, Hayleigh K.
27317f3f-f0d7-49b9-8d12-8d709413e2a7
Hammer, Matthew
e5be536d-fef1-48bd-a524-376bfbff8da0
Zhang, Shiqi
164faac3-cb84-421d-8732-3a67f383b9b7
Bruton, Alisha
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Hatsu, Irene E.
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Leung, Brenda
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McClure, Ryan
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Srikanth, Priya
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Farris, Yuliya
14653d4f-ddc1-4f1e-8a5c-057d00b4537a
Norby-Adams, Lydia
4dc06997-8c35-4998-9496-3cf4d753f819
Robinette, Lisa M.
018ff23a-4b18-474a-8da8-9fb845122179
Arnold, L. Eugene
ab3f1511-6228-42df-a38c-2a5e32a8d921
Swann, Jonathan R.
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Zhu, Jiangjiang
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Karstens, Lisa
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Johnstone, Jeanette M.
4e15ecb7-195c-4930-8105-dc07cd119451

Ast, Hayleigh K., Hammer, Matthew, Zhang, Shiqi, Bruton, Alisha, Hatsu, Irene E., Leung, Brenda, McClure, Ryan, Srikanth, Priya, Farris, Yuliya, Norby-Adams, Lydia, Robinette, Lisa M., Arnold, L. Eugene, Swann, Jonathan R., Zhu, Jiangjiang, Karstens, Lisa and Johnstone, Jeanette M. (2025) Gut microbiome changes with micronutrient supplementation in children with attention–deficit/hyperactivity disorder: the MADDY study. Gut Microbes, 17 (1), [2463570]. (doi:10.1080/19490976.2025.2463570).

Record type: Article

Abstract

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.

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Gut microbiome changes with micronutrient supplementation in children with attention deficit hyperactivity disorder the MADDY study - Version of Record
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Accepted/In Press date: 2 February 2025
Published date: 18 February 2025
Additional Information: Publisher Copyright: © 2025 The Author(s). Published with license by Taylor & Francis Group, LLC.
Keywords: ADHD, children, microbiome, micronutrients

Identifiers

Local EPrints ID: 503133
URI: http://eprints.soton.ac.uk/id/eprint/503133
ISSN: 1949-0976
PURE UUID: dc6d761b-c4cd-4ba5-8674-af2443b898be
ORCID for Jonathan R. Swann: ORCID iD orcid.org/0000-0002-6485-4529

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Date deposited: 22 Jul 2025 16:44
Last modified: 22 Aug 2025 02:28

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Contributors

Author: Hayleigh K. Ast
Author: Matthew Hammer
Author: Shiqi Zhang
Author: Alisha Bruton
Author: Irene E. Hatsu
Author: Brenda Leung
Author: Ryan McClure
Author: Priya Srikanth
Author: Yuliya Farris
Author: Lydia Norby-Adams
Author: Lisa M. Robinette
Author: L. Eugene Arnold
Author: Jiangjiang Zhu
Author: Lisa Karstens
Author: Jeanette M. Johnstone

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