Multi-level analysis of the gut–brain axis shows autism spectrum disorder-associated molecular and microbial profiles
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Published:2023-06-26
Issue:7
Volume:26
Page:1208-1217
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ISSN:1097-6256
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Container-title:Nature Neuroscience
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language:en
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Short-container-title:Nat Neurosci
Author:
Morton James T.ORCID, Jin Dong-Min, Mills Robert H., Shao YanORCID, 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.ORCID, Zurita María FernandaORCID, David Maude, Averina Olga V., Kovtun Alexey S., Noto AntonioORCID, Mussap Michele, Wang MingbangORCID, Frank Daniel N.ORCID, Li EllenORCID, Zhou WenhaoORCID, Fanos Vassilios, Danilenko Valery N., Wall Dennis P.ORCID, Cárdenas PaúlORCID, Baldeón Manuel E.ORCID, Jacquemont SébastienORCID, Koren Omry, Elliott EvanORCID, Xavier Ramnik J.ORCID, Mazmanian Sarkis K.ORCID, Knight RobORCID, Gilbert Jack A.ORCID, Donovan Sharon M., Lawley Trevor D.ORCID, Carpenter Bob, Bonneau Richard, Taroncher-Oldenburg GasparORCID
Abstract
AbstractAutism 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.
Funder
Eunice Kennedy Shriver National Institute of Child Health and Human Development Wellcome Trust National Natural Science Foundation of China European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme Israel Science Foundation
Publisher
Springer Science and Business Media LLC
Subject
General Neuroscience
Reference74 articles.
1. Lord, C. et al. Autism spectrum disorder. Nat. Rev. Dis. Primers 6, 5 (2020). 2. Satterstrom, F. K. et al. Large-scale exome sequencing study implicates both developmental and functional changes in the neurobiology of autism. Cell 180, 568–584 (2020). 3. Iakoucheva, L. M., Muotri, A. R. & Sebat, J. Getting to the cores of autism. Cell 178, 1287–1298 (2019). 4. Schumann, C. M. et al. The amygdala is enlarged in children but not adolescents with autism; the hippocampus is enlarged at all ages. J. Neurosci. 24, 6392–6401 (2004). 5. Lefter, R., Ciobica, A., Timofte, D., Stanciu, C. & Trifan, A. A descriptive review on the prevalence of gastrointestinal disturbances and their multiple associations in autism spectrum disorder. Medicina (Kaunas) 56, 11 (2019).
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