Autism spectrum disorders (ASD) are neuro-developmental disorders characterized by a lack of social skills, impaired communication and repetitive behaviours. The pathophysiological processes are still largely unknown but are thought to result from both genetic and environmental factors. Beside behavioural symptoms, a large majority of children with ASD also suffers from gastrointestinal (GI) symptoms. While the behavioural symptoms in ASD are linked to impaired brain neuronal connectivity, it is unknown whether GI symptoms stem from altered neuronal connectivity of the enteric nervous system. In addition, evidence unveiled dysbiosis of the gut microbiota as an important cofactor in ASD. Our group showed a potential causal relationship between dysbiotic gut microbiota, behavioural and GI symptoms. However, the mechanisms of microbiota-mediated effects on gut and brain are still largely unknown. We propose that extracellular vesicles (EVs) produced by bacterial microbiota serve as signaling cargo between microbiota and host organs. Our project has three main objectives. First, we will provide a comprehensive molecular profile of gut microbiota-derived EVs of children with ASD associated with clinical features. Second, we will study in cultures of enteric neurons and mouse models the effects of microbiota-derived EV from ASD children, as compared to controls, on enteric neuronal connectivity, GI functions and behaviour. Third, we will examine the interaction between host genetics microbiota-derived EV phenotype and activity on enteric neuronal connectivity, GI functions and behaviour. This proposal, based on innovative concepts, will expand our knowledge on the contribution of gut microbiota on ASD pathophysiological mechanisms. This understanding could open new avenues for diagnostics and therapeutics using EV-based treatments as “postbiotics”.