Shared immune and nutrient metabolism pathways between autism spectrum disorder and celiac disease: an in silico approach

Introduction: Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by social communication difficulties and repetitive behaviors. Emerging evidence suggests a potential link between ASD and celiac disease (CD), possibly mediated by immune dysregulation and nutrient deficiencies. This study explores the shared biological pathways between ASD and CD using an in silico approach.

Methods: Gene–disease associations for ASD and CD were retrieved from DisGeNET using MedGen Concept IDs (C1510586 and C0007570, respectively). An over-representation analysis (ORA) was conducted using GeneTrail 3.2 to identify significantly enriched biological pathways, which were then compared for overlap. A false discovery rate (FDR) < 0.05 was considered statistically significant.

Results: The gene–disease association analysis identified 536 ASD-related genes and 52 CD-related genes. The ORA revealed several shared biological pathways, including immune pathways, cellular metabolism, and micronutrient processing (e.g., folate, selenium, vitamin A). These findings suggest immune dysfunction and nutrient malabsorption as potential mechanistic links between ASD and CD.

Conclusions: The observed pathway overlap supports the hypothesis that immune dysregulation and metabolic disturbances contribute to both ASD and CD. Nutrient deficiencies, driven by CD-associated malabsorption, may exacerbate ASD symptoms. Additionally, sensory processing abnormalities in ASD could impact dietary choices, complicating gluten-free diet adherence. Future studies should validate these findings in clinical cohorts and explore dietary interventions, such as targeted supplementation, to mitigate ASD symptoms in individuals with CD.