Large-scale metagenomic analysis of oral microbiomes reveals markers for autism spectrum disorders
The 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<sup>-6</sup>) 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.
Authors
- Simone Montalbano (ORCID: https://orcid.org/0000-0002-9846-0560)
- Pamela Feliciano (ORCID: https://orcid.org/0000-0003-4266-1301)
- Jacob J. Michaelson (ORCID: https://orcid.org/0000-0001-9713-0992)
- Enrico Domenici (ORCID: https://orcid.org/0000-0001-7436-6919)
- Paolo Manghi (ORCID: https://orcid.org/0000-0003-0846-6529)
- LeeAnne Green Snyder (ORCID: https://orcid.org/0000-0001-9217-4865)
- Moreno Zolfo (ORCID: https://orcid.org/0000-0001-6661-4046)
- Albert García-Valiente (ORCID: https://orcid.org/0000-0002-0444-7251)
- Natalia Volfovsky (ORCID: https://orcid.org/0000-0003-4007-9035)
- Samuel Perini (ORCID: https://orcid.org/0000-0001-7524-151X)
- Jacob B. Hall
- Francesco Asnicar (ORCID: https://orcid.org/0000-0003-3732-1468)
- Davide Golzato (ORCID: https://orcid.org/0000-0002-2890-1527)
- Lucas G. Casten (ORCID: https://orcid.org/0000-0001-7690-6405)
- Levi Waldron (ORCID: https://orcid.org/0000-0003-2725-0694)
- Stefania Mattevi (ORCID: https://orcid.org/0000-0002-3141-3145)
- Samuele Cancellieri (ORCID: https://orcid.org/0000-0003-2537-6728)
- Nicola Segata (ORCID: https://orcid.org/0000-0002-1583-5794)
- Vitor Heidrich (ORCID: https://orcid.org/0000-0001-6617-9187)
- Simon Xu
- Andrew Maltez Thomas (ORCID: https://orcid.org/0000-0001-5789-3354)
- Mireia Valles‐Colomer (ORCID: https://orcid.org/0000-0002-1988-6054)
- Michele Filosi (ORCID: https://orcid.org/0000-0002-3872-347X)
Institutions
- Fondazione Edmund Mach (IT)
- The Graduate Center, CUNY (US)
- University of Iowa (US)
- Boston Children's Hospital (US)
- Okinawa Institute of Science and Technology Graduate University (JP)
- Universitat Pompeu Fabra (ES)
- University of Oslo (NO)
- University of Trento (IT)
- Copenhagen University Hospital (DK)
- Simons Foundation (US)
- Institute for Biomedicine (IT)
- European Institute of Oncology (IT)
- University of Brescia (IT)
Publication Details
- Journal
- Nature Communications
- Published
- 2024-11-11
- DOI
- https://doi.org/10.1038/s41467-024-53934-7
- Citations
- 26
- Primary Topic
- Autism Spectrum Disorder Research
- Type
- article
- Field-Weighted Citation Impact
- 8.91
Funders
- Simons Foundation Autism Research Initiative
- National Institutes of Health
- Horizon 2020 Framework Programme
- National Cancer Institute