Decoding the peripheral transcriptomic and meta-genomic response to music in autism spectrum disorder via saliva-based RNA sequencing.

Introduction: Behavioral interventions for autism spectrum disorder show variable outcomes, highlighting the need for complementary therapies. Music-based interventions are promising, yet their molecular mechanisms remain unclear. Saliva-based RNA sequencing (RNA-seq) provides a non-invasive framework to monitor neuroimmune and metabolic dynamics, but its application in autism remains underexplored. Methods: We explored the buccal transcriptional effects of music exposure in five individuals with autism (8-37 years; 60% female). To overcome saliva-specific limitations, we combined Poly-A selection and Human-Enriched protocols preparation methods to enhance human transcript detection and reproducibility while capturing microbial signals. Results: Individually, each dataset revealed a few differentially expressed genes, but integrated analysis improved biological resolution. Consistently modulated genes included Conclusion: Saliva-based RNA-seq can stably capture transcriptomic and microbial responses to behavioral stimuli. Music exposure modulates neuroimmune pathways relevant to autism, supporting the biological plausibility of music therapy and demonstrating saliva-based RNA-seq as a viable, non-invasive tool for monitoring intervention outcomes.