Manghi, PaoloVallès Colomer, MireiaDomenici, Enrico2025-01-142025-01-142024Manghi P, Filosi M, Zolfo M, Casten LG, Garcia-Valiente A, Mattevi S, et al. Large-scale metagenomic analysis of oral microbiomes reveals markers for autism spectrum disorders. Nat Commun. 2024 Nov 11;15(1):9743. DOI: 10.1038/s41467-024-53934-72041-1723http://hdl.handle.net/10230/69122The link between the oral microbiome and neurodevelopmental disorders remains a compelling hypothesis, still requiring confirmation in large-scale datasets. Leveraging over 7000 whole-genome sequenced salivary samples from 2025 US families with children diagnosed with autism spectrum disorders (ASD), our cross-sectional study shows that the oral microbiome composition can discriminate ASD subjects from neurotypical siblings (NTs, AUC = 0.66), with 108 differentiating species (q < 0.005). The relative abundance of these species is highly correlated with cognitive impairment as measured by Full-Scale Intelligence Quotient (IQ). ASD children with IQ < 70 also exhibit lower microbiome strain sharing with parents (p < 10-6) with respect to NTs. A two-pronged functional enrichment analysis suggests the contribution of enzymes from the serotonin, GABA, and dopamine degradation pathways to the distinct microbial community compositions observed between ASD and NT samples. Although measures of restrictive eating diet and proxies of oral hygiene show relatively minor effects on the microbiome composition, the observed associations with ASD and IQ may still represent unaccounted-for underlying differences in lifestyle among groups. While causal relationships could not be established, our study provides substantial support to the investigation of oral microbiome biomarkers in ASD.application/pdfeng© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.info:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41467-024-53934-7Autism spectrum disordersMetagenomicsinfo:eu-repo/semantics/openAccess