Interaction of the Gut Microbiota and the Enteric Nervous System: Implications in Gastrointestinal Disorders Associated With Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction, restricted interests, and repetitive behaviors. In addition to these core behavioral symptoms, gastrointestinal (GI) disorders are frequently reported, ranging from severe constipation to diarrhea. The links between ASD and gut dysfunction are further supported by alterations in gut microbiota composition and in bacteria-derived metabolites. As the intrinsic nervous system of the digestive tract, the enteric nervous system (ENS) plays a central role in gut physiology by exerting neuronal control on several gut functions, including motility. Located at the interface between the gut microbiota and intestinal function, the ENS may play a key role in the GI symptoms associated with ASD, as demonstrated in several mouse models. This review aims to summarize the interconnected alterations of the gut microbiota and the ENS in ASD, with a particular focus on the microbiota-derived mediators that are altered in ASD, among patients and animal models, and that may affect ENS development and function. By highlighting these interactions, this review seeks to provide new insights on the digestive pathophysiology of ASD, which may also contribute to the severity of behavioral symptoms.