Purpose <p>The brain-gut-microbiome (BGM) system encompasses a bidirectional communication network between the gut microbiome and the brain and plays a critical role in maintaining gut function and modulating behavior. Here, we specifically focus on the interactions between sensory over-responsivity (SOR), a common phenotype in Autism Spectrum Disorder (ASD), and the BGM system and discuss potential mechanisms underlying these interactions.</p> Methods <p>We examine key constructs and frameworks related to sensory processing, autism, and the BGM system, synthesize literature to identify knowledge gaps, and propose a model linking the BGM system and SOR in autism.</p> Results <p>Grounded in prior literature, we propose a conceptual model involving the brain, the gut microbiome, and SOR in autism. In this model sensory features of foods commonly associated with SOR contribute to atypical eating behaviors, resulting in differences in dietary intake, which in turn affect the gut and oral microbiomes. The gut microbiome can impact neural activity and brain structure via the connection between the gut and the brain, further contributing to SOR.</p> Conclusion <p>The interdisciplinary nature of this topic is emphasized, bridging research from neuroscience, microbiology, pediatrics, nutrition, psychology, and occupational therapy/occupational science. Reflecting on the intersection of autism characteristics and microbiome health, this analysis offers critical insights for research and clinical practice.</p>