Digestive Neurobiology in Autism: From Enteric and Central Nervous System Interactions to Shared Genetic Pathways

Social communication difficulties characterize autism spectrum disorders (ASD). Gastrointestinal (GI) symptoms are more common in ASD than in the general population. The identification of GI problems in individuals with ASD is challenging due to their altered pain perception and irregular behaviors. Importantly, GI symptoms and ASD can potentially aggravate each other. However, it is unclear if GI problems cause ASD symptoms or vice versa. A crosstalk between the digestive system, gut microbiota, and the central and enteric nervous systems (CNS and ENS, respectively) has been repeatedly reported. The ENS regulates the GI tract with the CNS and the autonomic nervous system (ANS), as well as independently through specific neural circuits. Several mechanisms contribute to GI problems in ASD, including genetic mutations that affect the ENS, dysregulation of the ANS, alterations in gut microbiota, unhealthy dietary preferences, and changes in metabolomic profiles. Furthermore, studies have shown molecular and cellular differences in the GI biopsy of children with and without ASD. These findings highlight the unique nature of GI issues in ASD, underscoring the importance of further investigating the changes that occur in the digestive system and ENS in ASD models.