TY - JOUR
T1 - Multi-level analysis of the gut–brain axis shows autism spectrum disorder-associated molecular and microbial profiles
AU - Morton, James T.
AU - Jin, Dong Min
AU - Mills, Robert H.
AU - Shao, Yan
AU - Rahman, Gibraan
AU - McDonald, Daniel
AU - Zhu, Qiyun
AU - Balaban, Metin
AU - Jiang, Yueyu
AU - Cantrell, Kalen
AU - Gonzalez, Antonio
AU - Carmel, Julie
AU - Frankiensztajn, Linoy Mia
AU - Martin-Brevet, Sandra
AU - Berding, Kirsten
AU - Needham, Brittany D.
AU - Zurita, María Fernanda
AU - David, Maude
AU - Averina, Olga V.
AU - Kovtun, Alexey S.
AU - Noto, Antonio
AU - Mussap, Michele
AU - Wang, Mingbang
AU - Frank, Daniel N.
AU - Li, Ellen
AU - Zhou, Wenhao
AU - Fanos, Vassilios
AU - Danilenko, Valery N.
AU - Wall, Dennis P.
AU - Cárdenas, Paúl
AU - Baldeón, Manuel E.
AU - Jacquemont, Sébastien
AU - Koren, Omry
AU - Elliott, Evan
AU - Xavier, Ramnik J.
AU - Mazmanian, Sarkis K.
AU - Knight, Rob
AU - Gilbert, Jack A.
AU - Donovan, Sharon M.
AU - Lawley, Trevor D.
AU - Carpenter, Bob
AU - Bonneau, Richard
AU - Taroncher-Oldenburg, Gaspar
N1 - J.T.M. was funded by the intramural research program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Y.S. and T.D.L. are supported by the Wellcome Trust (WT206194). M.W. is supported by the National Natural Science Foundation of China (program no. 82071733) and Shanghai talent development funding (no. 2020115). E.E. is supported by Israel Science Foundation grant 818/17 and a research grant provided by Teva Pharmaceuticals under their support of the Azrieli Faculty of Medicine. O.K. is supported by the European Research Council (ERC) under the European Union\u2019s Horizon 2020 Research and Innovation Program (grant agreement ERC-2020-COG no. 101001355). We would like to thank A. Packer, P. Wang, N. Volfovsky, K. Martin and J. Spiro for their critical review of the manuscript. We would like to thank S. Mirarab for feedback on the construction of the Greengenes2 and Web of Life databases. We would like to thank A. Amir for insights on processing shotgun metagenomics and 16S sequencing data using the GetData software package. We would also like to thank K. Liu, H. Sherman and X.-J. Kong for insightful discussions.
PY - 2023/7
Y1 - 2023/7
N2 - 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.
AB - 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.
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U2 - 10.1038/s41593-023-01361-0
DO - 10.1038/s41593-023-01361-0
M3 - Article
C2 - 37365313
AN - SCOPUS:85162935526
SN - 1097-6256
VL - 26
SP - 1208
EP - 1217
JO - Nature Neuroscience
JF - Nature Neuroscience
IS - 7
ER -