The Vitamin D-Gut-Brain Axis in Autism Spectrum Disorder: A Bidirectional Crosstalk

Abstract

Abstract Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder arising from the interaction of genetic and environmental triggers. In recent years, vitamin D deficiency and gut microbiota dysbiosis have emerged as two pivotal environment-related factors in ASD pathogenesis. Rather than acting independently, these factors jointly participate in the onset and progression of ASD through intricate bidirectional interaction mechanisms. This article presents a narrative review that summarizes the current research progress regarding the association between vitamin D deficiency and gut microbiota dysbiosis in ASD. Mechanistically, vitamin D modulates the gut-brain axis across multiple levels, including gut microbiota composition, intestinal barrier function, intestinal inflammation, bacterial translocation, microbial metabolites, blood-brain barrier integrity and neuroinflammation. In turn, the gut microbiota influences vitamin D metabolism and bioactivity through short-chain fatty acids, establishing a bidirectional vitamin D-gut-brain axis. This axis likely contributes to ASD phenotypes by regulating neuroinflammation, gut-brain crosstalk and neurodevelopmental processes. Notably, most available evidence in this field is derived from preclinical studies, while relevant clinical evidence remains limited. Future studies should focus on dissecting the underlying molecular crosstalk and developing personalized intervention strategies targeting vitamin D status and microbial signatures.