biostudies-literatureMorton JTEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentEuropean Research CouncilIsrael Science FoundationNational Natural Science Foundation of ChinaWellcome Trust1208-1217https://www.ebi.ac.uk/biostudies/studies/S-EPMC10322709biostudies-literatureUnknown26(7)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 tNature neuroscienceMulti-level analysis of the gut-brain axis shows autism spectrum disorder-associated molecular and microbial profiles.PMC10322709WT20619410100135582071733)818/17McDonald DDanilenko VNElliott EFrankiensztajn LMLawley TDCardenas PDonovan SMJiang YWang MNoto AShao YKoren OMorton JTBalaban MAverina OVBonneau RMazmanian SKJin DMDavid MJacquemont SZurita MFNeedham BDMills RHFrank DNWall DPLi ECantrell KTaroncher-Oldenburg GXavier RJCarmel JRahman GMartin-Brevet SZhou WGilbert JAFanos VKnight RKovtun ASCarpenter BMussap MBaldeon MEBerding KZhu QGonzalez AfalseMulti-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 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 t2023-01-01T00:00:00Z2023 Jul2025-06-01T00:14:31.669Z2025-06-01T00:14:31.669ZS-EPMC103227093736531310.1038/s41593-023-01361-0