Large-scale metagenomic analysis of oral microbiomes reveals markers for autism spectrum disorders

Nature Communications volume  15, Article number: 9743 (2024 ) Cite this article

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 < 10−6) 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.

Autism spectrum disorders (ASD)1 are neurodevelopmental impairments involving the cognitive, emotional, relational, and behavioural spheres2,3,4. ASD children show repetitive behaviours and sensory hyper-sensibility5,6. Estimates of ASD prevalence per 1000 children in the US range from 18.5 to 27.67. ASD are thought to arise from the interaction between genetic and environmental factors3,8,9,10,11,12, with small-effect and de novo variants contributing to disease risk13,14,15,16. Although more than 180 ASD-implicated genes have been identified from joint analysis of protein-truncating variants, missense variants and copy number variants16, they represent only a fraction of the estimated up to 1000 genes possibly involved in ASD aetiology17,18. In addition to the genetic makeup inherited from the parents and de novo variants, the microbial community acquired at birth and shaped during childhood19 has been proposed as an element for a better understanding of ASD pathophysiology20,21,22.

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