Multi-level analysis of the gut–brain axis shows autism spectrum disorder-associated molecular and microbial profiles

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by heterogeneous cognitive, behavioral and communication impairments. Disruption of the gut–brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, we developed a Ba...

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Published in:Nature neuroscience Vol. 26; no. 7; pp. 1208 - 1217
Main Authors: Morton, James T., Jin, Dong-Min, Mills, Robert H., Shao, Yan, Rahman, Gibraan, McDonald, Daniel, Zhu, Qiyun, Balaban, Metin, Jiang, Yueyu, Cantrell, Kalen, Gonzalez, Antonio, Carmel, Julie, Frankiensztajn, Linoy Mia, Martin-Brevet, Sandra, Berding, Kirsten, Needham, Brittany D., Zurita, María Fernanda, David, Maude, Averina, Olga V., Kovtun, Alexey S., Noto, Antonio, Mussap, Michele, Wang, Mingbang, Frank, Daniel N., Li, Ellen, Zhou, Wenhao, Fanos, Vassilios, Danilenko, Valery N., Wall, Dennis P., Cárdenas, Paúl, Baldeón, Manuel E., Jacquemont, Sébastien, Koren, Omry, Elliott, Evan, Xavier, Ramnik J., Mazmanian, Sarkis K., Knight, Rob, Gilbert, Jack A., Donovan, Sharon M., Lawley, Trevor D., Carpenter, Bob, Bonneau, Richard, Taroncher-Oldenburg, Gaspar
Format: Journal Article
Language:English
Published: New York Nature Publishing Group US 01.07.2023
Nature Publishing Group
Subjects:
631/114/2401
631/208/212
631/326
631/378/1689/1373
Algorithms
Amino acids
Animal Genetics and Genomics
Autism
Autism Spectrum Disorder - genetics
Autism Spectrum Disorder - metabolism
Bayes Theorem
Bayesian analysis
Behavioral Sciences
Biological Techniques
Biomedical and Life Sciences
Biomedicine
Brain
Brain architecture
Brain-Gut Axis
Carbohydrates
Cognitive ability
Cross-Sectional Studies
Cytokines
Datasets
Diet
Disruption
Gastrointestinal Microbiome - genetics
Gene expression
Gut-brain axis
Heterogeneity
Humans
Inflammation
Lipids
Metabolomics
Microbiomes
Microorganisms
Neurobiology
Neurodevelopmental disorders
Neurosciences
Phenotypes
Reproducibility
Reproducibility of Results
ISSN:1097-6256, 1546-1726, 1546-1726
Online Access:Get full text
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Summary:Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by heterogeneous cognitive, behavioral and communication impairments. Disruption of the gut–brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, we developed a Bayesian differential ranking algorithm to identify ASD-associated molecular and taxa profiles across 10 cross-sectional microbiome datasets and 15 other datasets, including dietary patterns, metabolomics, cytokine profiles and human brain gene expression profiles. We found a functional architecture along the GBA that correlates with heterogeneity of ASD phenotypes, and it is characterized by ASD-associated amino acid, carbohydrate and lipid profiles predominantly encoded by microbial species in the genera Prevotella , Bifidobacterium , Desulfovibrio and Bacteroides and correlates with brain gene expression changes, restrictive dietary patterns and pro-inflammatory cytokine profiles. The functional architecture revealed in age-matched and sex-matched cohorts is not present in sibling-matched cohorts. We also show a strong association between temporal changes in microbiome composition and ASD phenotypes. In summary, we propose a framework to leverage multi-omic datasets from well-defined cohorts and investigate how the GBA influences ASD. Autism spectrum disorder (ASD) is characterized by heterogeneous phenotypes. Disruption of the gut–brain axis (GBA) has been implicated in ASD although with limited reproducibility across studies. In this study, the authors propose a framework to leverage multi-omic datasets and investigate how the GBA influences ASD.
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ISSN:1097-6256
1546-1726
1546-1726
DOI:10.1038/s41593-023-01361-0