Autism-related dietary preferences mediate autism-gut microbiome associations

Chloe X Yap¹, Anjali K Henders², Gail A Alvares³, David L A Wood⁴, Lutz Krause⁴, Gene W Tyson⁵, Restuadi Restuadi⁶, Leanne Wallace², Tiana McLaren², Narelle K Hansell⁷, Dominique Cleary³, Rachel Grove⁸, Claire Hafekost³, Alexis Harun³, Helen Holdsworth⁹, Rachel Jellett¹⁰, Feroza Khan¹¹, Lauren P Lawson¹⁰, Jodie Leslie³, Mira Levis Frenk⁹, Anne Masi¹¹, Nisha E Mathew¹¹, Melanie Muniandy¹⁰, Michaela Nothard⁹, Jessica L Miller⁷, Lorelle Nunn⁶, Gerald Holtmann¹², Lachlan T Strike⁷, Greig I de Zubicaray¹³, Paul M Thompson¹⁴, Katie L McMahon¹⁵, Margaret J Wright¹⁶, Peter M Visscher⁶, Paul A Dawson¹⁷, Cheryl Dissanayake¹⁰, Valsamma Eapen¹⁸, Helen S Heussler¹⁹, Allan F McRae⁶, Andrew J O Whitehouse³, Naomi R Wray²⁰, Jacob Gratten²¹

Affiliations

¹ Mater Research Institute, The University of Queensland, Woolloongabba, Queensland 4102, Australia; Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Queensland 4068, Australia.
² Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Queensland 4068, Australia.
³ Telethon Kids Institute, The University of Western Australia, Nedlands, Western Australia 6009, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Queensland 4068, Australia.
⁴ Microba Life Sciences, Brisbane, Queensland 4000, Australia.
⁵ Microba Life Sciences, Brisbane, Queensland 4000, Australia; Centre for Microbiome Research, School of Biomedical Sciences, Queensland University of Technology, Translational Research Institute, Woolloongabba, Queensland 4102, Australia.
⁶ Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.
⁷ Queensland Brain Institute, The University of Queensland, St Lucia, Queensland 4072, Australia.
⁸ Faculty of Health, University of Technology Sydney, Sydney, New South Wales 2007, Australia; School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2052, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Queensland 4068, Australia.
⁹ Mater Research Institute, The University of Queensland, Woolloongabba, Queensland 4102, Australia; Child Health Research Centre, The University of Queensland, South Brisbane, Queensland 4101, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Queensland 4068, Australia.
¹⁰ Olga Tennison Autism Research Centre, La Trobe University, Bundoora, Victoria 3086, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Queensland 4068, Australia.
¹¹ School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2052, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Queensland 4068, Australia.
¹² Faculty of Medicine and Faculty of Health and Behavioural Science, University of Queensland, St Lucia, Queensland 4072, Australia; Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Woolloongabba, Queensland 4102, Australia.
¹³ School of Psychology and Counselling, Faculty of Health, Queensland University of Technology, Kelvin Grove, Queensland 4059, Australia.
¹⁴ Imaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging & Informatics, Keck School of Medicine, University of Southern California, Los Angeles, USA.
¹⁵ School of Clinical Sciences, Centre for Biomedical Technologies, Queensland University of Technology, Brisbane, Queensland 4000, Australia.
¹⁶ Queensland Brain Institute, The University of Queensland, St Lucia, Queensland 4072, Australia; Centre for Advanced Imaging, The University of Queensland, St Lucia, Queensland 4072, Australia.
¹⁷ Mater Research Institute, The University of Queensland, Woolloongabba, Queensland 4102, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Queensland 4068, Australia.
¹⁸ School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2052, Australia; Academic Unit of Child Psychiatry South West Sydney, Ingham Institute, Liverpool Hospital, Sydney, New South Wales, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Queensland 4068, Australia.
¹⁹ Child Health Research Centre, The University of Queensland, South Brisbane, Queensland 4101, Australia; Child Development Program, Children's Health Queensland, South Brisbane, Queensland 4101, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Queensland 4068, Australia.
²⁰ Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia; Queensland Brain Institute, The University of Queensland, St Lucia, Queensland 4072, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Queensland 4068, Australia.
²¹ Mater Research Institute, The University of Queensland, Woolloongabba, Queensland 4102, Australia; Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Queensland 4068, Australia. Electronic address: jacob.gratten@mater.uq.edu.au.

PMID: 34767757
DOI: 10.1016/j.cell.2021.10.015

Free article

Autism-related dietary preferences mediate autism-gut microbiome associations

Chloe X Yap et al. Cell. 2021.

Free article

. 2021 Nov 24;184(24):5916-5931.e17.

doi: 10.1016/j.cell.2021.10.015. Epub 2021 Nov 11.

Authors

Affiliations

¹ Mater Research Institute, The University of Queensland, Woolloongabba, Queensland 4102, Australia; Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Queensland 4068, Australia.
² Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Queensland 4068, Australia.
³ Telethon Kids Institute, The University of Western Australia, Nedlands, Western Australia 6009, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Queensland 4068, Australia.
⁴ Microba Life Sciences, Brisbane, Queensland 4000, Australia.
⁵ Microba Life Sciences, Brisbane, Queensland 4000, Australia; Centre for Microbiome Research, School of Biomedical Sciences, Queensland University of Technology, Translational Research Institute, Woolloongabba, Queensland 4102, Australia.
⁶ Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia.
⁷ Queensland Brain Institute, The University of Queensland, St Lucia, Queensland 4072, Australia.
⁸ Faculty of Health, University of Technology Sydney, Sydney, New South Wales 2007, Australia; School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2052, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Queensland 4068, Australia.
⁹ Mater Research Institute, The University of Queensland, Woolloongabba, Queensland 4102, Australia; Child Health Research Centre, The University of Queensland, South Brisbane, Queensland 4101, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Queensland 4068, Australia.
¹⁰ Olga Tennison Autism Research Centre, La Trobe University, Bundoora, Victoria 3086, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Queensland 4068, Australia.
¹¹ School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2052, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Queensland 4068, Australia.
¹² Faculty of Medicine and Faculty of Health and Behavioural Science, University of Queensland, St Lucia, Queensland 4072, Australia; Department of Gastroenterology & Hepatology, Princess Alexandra Hospital, Woolloongabba, Queensland 4102, Australia.
¹³ School of Psychology and Counselling, Faculty of Health, Queensland University of Technology, Kelvin Grove, Queensland 4059, Australia.
¹⁴ Imaging Genetics Center, Mark & Mary Stevens Institute for Neuroimaging & Informatics, Keck School of Medicine, University of Southern California, Los Angeles, USA.
¹⁵ School of Clinical Sciences, Centre for Biomedical Technologies, Queensland University of Technology, Brisbane, Queensland 4000, Australia.
¹⁶ Queensland Brain Institute, The University of Queensland, St Lucia, Queensland 4072, Australia; Centre for Advanced Imaging, The University of Queensland, St Lucia, Queensland 4072, Australia.
¹⁷ Mater Research Institute, The University of Queensland, Woolloongabba, Queensland 4102, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Queensland 4068, Australia.
¹⁸ School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, New South Wales 2052, Australia; Academic Unit of Child Psychiatry South West Sydney, Ingham Institute, Liverpool Hospital, Sydney, New South Wales, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Queensland 4068, Australia.
¹⁹ Child Health Research Centre, The University of Queensland, South Brisbane, Queensland 4101, Australia; Child Development Program, Children's Health Queensland, South Brisbane, Queensland 4101, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Queensland 4068, Australia.
²⁰ Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia; Queensland Brain Institute, The University of Queensland, St Lucia, Queensland 4072, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Queensland 4068, Australia.
²¹ Mater Research Institute, The University of Queensland, Woolloongabba, Queensland 4102, Australia; Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Queensland 4068, Australia. Electronic address: jacob.gratten@mater.uq.edu.au.

PMID: 34767757
DOI: 10.1016/j.cell.2021.10.015

Erratum in

Autism-related dietary preferences mediate autism-gut microbiome associations.
Yap CX, Henders AK, Alvares GA, Wood DLA, Krause L, Tyson GW, Restuadi R, Wallace L, McLaren T, Hansell NK, Cleary D, Grove R, Hafekost C, Harun A, Holdsworth H, Jellett R, Khan F, Lawson LP, Leslie J, Frenk ML, Masi A, Mathew NE, Muniandy M, Nothard M, Miller JL, Nunn L, Holtmann G, Strike LT, de Zubicaray GI, Thompson PM, McMahon KL, Wright MJ, Visscher PM, Dawson PA, Dissanayake C, Eapen V, Heussler HS, McRae AF, Whitehouse AJO, Wray NR, Gratten J. Yap CX, et al. Cell. 2024 Jan 18;187(2):495-510. doi: 10.1016/j.cell.2023.12.001. Cell. 2024. PMID: 38242089 No abstract available.

Abstract

There is increasing interest in the potential contribution of the gut microbiome to autism spectrum disorder (ASD). However, previous studies have been underpowered and have not been designed to address potential confounding factors in a comprehensive way. We performed a large autism stool metagenomics study (n = 247) based on participants from the Australian Autism Biobank and the Queensland Twin Adolescent Brain project. We found negligible direct associations between ASD diagnosis and the gut microbiome. Instead, our data support a model whereby ASD-related restricted interests are associated with less-diverse diet, and in turn reduced microbial taxonomic diversity and looser stool consistency. In contrast to ASD diagnosis, our dataset was well powered to detect microbiome associations with traits such as age, dietary intake, and stool consistency. Overall, microbiome differences in ASD may reflect dietary preferences that relate to diagnostic features, and we caution against claims that the microbiome has a driving role in ASD.

Keywords: autism; autism spectrum disorder; brain-gut-microbiome axis; diet; gut microbiome; metagenomics; restricted and repetitive behaviors and interests; stool consistency.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests David L.A. Wood and Lutz Krause are employees of Microba Life Sciences. Gene W. Tyson is a co-founder and director of Microba Life Sciences. Gerald Holtmann is on the advisory board of Servatus Biopharmaceuticals. The other authors declare no competing interests.

Comment in

Diet underlying autism-microbiome association.
Hofer U. Hofer U. Nat Rev Microbiol. 2022 Feb;20(2):63. doi: 10.1038/s41579-021-00670-0. Nat Rev Microbiol. 2022. PMID: 34824464 No abstract available.
Gut microbiome and autism spectrum disorder.
Kotsiliti E. Kotsiliti E. Nat Rev Gastroenterol Hepatol. 2022 Jan;19(1):6. doi: 10.1038/s41575-021-00564-9. Nat Rev Gastroenterol Hepatol. 2022. PMID: 34857938 No abstract available.
Dietary diversity contributes to microbiome associations in autism.
Johnson AJ, Howell BR. Johnson AJ, et al. Cell Metab. 2021 Dec 7;33(12):2311-2313. doi: 10.1016/j.cmet.2021.11.008. Cell Metab. 2021. PMID: 34879238 Free PMC article.
Diet drives altered microbiota in autism.
Welberg L. Welberg L. Nat Neurosci. 2022 Jan;25(1):2. doi: 10.1038/s41593-021-00990-7. Nat Neurosci. 2022. PMID: 34992290 No abstract available.
Diet, microbe, and autism: Cause or consequence?
Li G, Song B, Wang C, Tang D, Li K, He X, Cao Y. Li G, et al. Cell Host Microbe. 2022 Jan 12;30(1):5-7. doi: 10.1016/j.chom.2021.12.018. Cell Host Microbe. 2022. PMID: 35026135
Are changes in the gut microbiome a contributor or consequence of autism-why not both?
Özcan E, Hsiao EY. Özcan E, et al. Cell Rep Med. 2022 Jan 18;3(1):100505. doi: 10.1016/j.xcrm.2021.100505. eCollection 2022 Jan 18. Cell Rep Med. 2022. PMID: 35106514 Free PMC article.

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
- Elsevier Science
Other Literature Sources
- H1 Connect - Access expert opinions and insights on biomedical research.
- The Lens - Patent Citations Database

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Autism-related dietary preferences mediate autism-gut microbiome associations

Affiliations

Autism-related dietary preferences mediate autism-gut microbiome associations

Authors

Affiliations

Erratum in

Abstract

Conflict of interest statement

Comment in

Publication types

MeSH terms

LinkOut - more resources

Full Text Sources

Other Literature Sources