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Microbiome-Specific Statistical Modeling Identifies Interplay Between Gastrointestinal Microbiome and Neurobehavioral Outcomes in Patients With Autism: A Case Control Study

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with unclear mechanisms of pathogenesis. Gastrointestinal microbiome alterations were found to correlate with ASD core symptoms, but its specific role in ASD pathogenesis has not been determined. In this study, we used a case-control st...

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Autores principales: Huang, Minshi, Liu, Jun, Liu, Kevin, Chen, Jierong, Wei, Zhen, Feng, Zhe, Wu, Yuyu, Fong, Michelle, Tian, Ruiyi, Wang, Bryan, Budjan, Christoph, Zhuang, Patrick, Wan, Guobin, Kong, Xue-Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563626/
https://www.ncbi.nlm.nih.gov/pubmed/34744810
http://dx.doi.org/10.3389/fpsyt.2021.682454
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author Huang, Minshi
Liu, Jun
Liu, Kevin
Chen, Jierong
Wei, Zhen
Feng, Zhe
Wu, Yuyu
Fong, Michelle
Tian, Ruiyi
Wang, Bryan
Budjan, Christoph
Zhuang, Patrick
Wan, Guobin
Kong, Xue-Jun
author_facet Huang, Minshi
Liu, Jun
Liu, Kevin
Chen, Jierong
Wei, Zhen
Feng, Zhe
Wu, Yuyu
Fong, Michelle
Tian, Ruiyi
Wang, Bryan
Budjan, Christoph
Zhuang, Patrick
Wan, Guobin
Kong, Xue-Jun
author_sort Huang, Minshi
collection PubMed
description Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with unclear mechanisms of pathogenesis. Gastrointestinal microbiome alterations were found to correlate with ASD core symptoms, but its specific role in ASD pathogenesis has not been determined. In this study, we used a case-control strategy that simultaneously compared the ASD gastrointestinal microbiome with that from age-sex matched controls and first-degree relative controls, using a statistical framework accounting for confounders such as age. Enterobacteriaceae (including Escherichia/Shigella) and Phyllobacterium were significantly enriched in the ASD group, with their relative abundances all following a pattern of ASD > first degree relative control > healthy control, consistent with our hypothesis of living environment and shared microbial and immunological exposures as key drivers of ASD gastrointestinal microbiome dysbiosis. Using multivariable omnibus testing, we identified clinical factors including ADOS scores, dietary habits, and gastrointestinal symptoms that covary with overall microbiome structure within the ASD cohort. A microbiome-specific multivariate modeling approach (MaAsLin2) demonstrated microbial taxa, such as Lachnoclostridium and Tyzzerella, are significantly associated with ASD core symptoms measured by ADOS. Finally, we identified alterations in predicted biological functions, including tryptophan and tyrosine biosynthesis/metabolism potentially relevant to the pathophysiology of the gut-brain-axis. Overall, our results identified gastrointestinal microbiome signature changes in patients with ASD, highlighted associations between gastrointestinal microbiome and clinical characteristics related to the gut-brain axis and identified contributors to the heterogeneity of gastrointestinal microbiome within the ASD population.
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spelling pubmed-85636262021-11-04 Microbiome-Specific Statistical Modeling Identifies Interplay Between Gastrointestinal Microbiome and Neurobehavioral Outcomes in Patients With Autism: A Case Control Study Huang, Minshi Liu, Jun Liu, Kevin Chen, Jierong Wei, Zhen Feng, Zhe Wu, Yuyu Fong, Michelle Tian, Ruiyi Wang, Bryan Budjan, Christoph Zhuang, Patrick Wan, Guobin Kong, Xue-Jun Front Psychiatry Psychiatry Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with unclear mechanisms of pathogenesis. Gastrointestinal microbiome alterations were found to correlate with ASD core symptoms, but its specific role in ASD pathogenesis has not been determined. In this study, we used a case-control strategy that simultaneously compared the ASD gastrointestinal microbiome with that from age-sex matched controls and first-degree relative controls, using a statistical framework accounting for confounders such as age. Enterobacteriaceae (including Escherichia/Shigella) and Phyllobacterium were significantly enriched in the ASD group, with their relative abundances all following a pattern of ASD > first degree relative control > healthy control, consistent with our hypothesis of living environment and shared microbial and immunological exposures as key drivers of ASD gastrointestinal microbiome dysbiosis. Using multivariable omnibus testing, we identified clinical factors including ADOS scores, dietary habits, and gastrointestinal symptoms that covary with overall microbiome structure within the ASD cohort. A microbiome-specific multivariate modeling approach (MaAsLin2) demonstrated microbial taxa, such as Lachnoclostridium and Tyzzerella, are significantly associated with ASD core symptoms measured by ADOS. Finally, we identified alterations in predicted biological functions, including tryptophan and tyrosine biosynthesis/metabolism potentially relevant to the pathophysiology of the gut-brain-axis. Overall, our results identified gastrointestinal microbiome signature changes in patients with ASD, highlighted associations between gastrointestinal microbiome and clinical characteristics related to the gut-brain axis and identified contributors to the heterogeneity of gastrointestinal microbiome within the ASD population. Frontiers Media S.A. 2021-10-20 /pmc/articles/PMC8563626/ /pubmed/34744810 http://dx.doi.org/10.3389/fpsyt.2021.682454 Text en Copyright © 2021 Huang, Liu, Liu, Chen, Wei, Feng, Wu, Fong, Tian, Wang, Budjan, Zhuang, Wan and Kong. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Psychiatry
Huang, Minshi
Liu, Jun
Liu, Kevin
Chen, Jierong
Wei, Zhen
Feng, Zhe
Wu, Yuyu
Fong, Michelle
Tian, Ruiyi
Wang, Bryan
Budjan, Christoph
Zhuang, Patrick
Wan, Guobin
Kong, Xue-Jun
Microbiome-Specific Statistical Modeling Identifies Interplay Between Gastrointestinal Microbiome and Neurobehavioral Outcomes in Patients With Autism: A Case Control Study
title Microbiome-Specific Statistical Modeling Identifies Interplay Between Gastrointestinal Microbiome and Neurobehavioral Outcomes in Patients With Autism: A Case Control Study
title_full Microbiome-Specific Statistical Modeling Identifies Interplay Between Gastrointestinal Microbiome and Neurobehavioral Outcomes in Patients With Autism: A Case Control Study
title_fullStr Microbiome-Specific Statistical Modeling Identifies Interplay Between Gastrointestinal Microbiome and Neurobehavioral Outcomes in Patients With Autism: A Case Control Study
title_full_unstemmed Microbiome-Specific Statistical Modeling Identifies Interplay Between Gastrointestinal Microbiome and Neurobehavioral Outcomes in Patients With Autism: A Case Control Study
title_short Microbiome-Specific Statistical Modeling Identifies Interplay Between Gastrointestinal Microbiome and Neurobehavioral Outcomes in Patients With Autism: A Case Control Study
title_sort microbiome-specific statistical modeling identifies interplay between gastrointestinal microbiome and neurobehavioral outcomes in patients with autism: a case control study
topic Psychiatry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563626/
https://www.ncbi.nlm.nih.gov/pubmed/34744810
http://dx.doi.org/10.3389/fpsyt.2021.682454
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