Microbiome’s effect on white matter in autism

Autism spectrum disorder (ASD) is characterized by deficits in social communication and restricted, repetitive behavioral patterns. Although other physiological presentations in individuals with ASD are heterogeneous, neuroimaging studies have consistently revealed a developmental pattern of initial white matter hypermyelination followed by reduced myelination compared with typically developing peers. Multiple studies have demonstrated that core ASD symptoms, including impairments in social skills, language acquisition, learning capabilities, motor performance, and sensory processing, correlate significantly with white matter dysregulation measured through diffusion tensor imaging (DTI). Longitudinal studies have shown that decreased gut microbiome diversity, particularly reductions in beneficial bacteria such as Bifidobacterium and Lactobacillus, correlates with symptom severity. Emerging mechanistic evidence suggests bidirectional relationships between microbiome composition and white matter development, both directly through metabolites like short-chain fatty acids (SCFAs) that regulate oligodendrocyte function and subsequent myelination, and indirectly through modulation of neuroinflammatory pathways. By integrating molecular-level gut physiology findings with macro-level brain imaging data, we may identify novel therapeutic approaches targeting the gut-brain axis in ASD management.