Autism spectrum disorders and the gastrointestinal tract: insights into mechanisms and clinical relevance

Autism spectrum disorders (ASDs) are recognized as central neurodevelopmental disorders diagnosed by impairments in social interactions, communication and repetitive behaviours. The recognition of ASD as a central nervous system (CNS)-mediated neurobehavioural disorder has led most of the research in ASD to be focused on the CNS. However, gastrointestinal function is also likely to be affected owing to the neural mechanistic nature of ASD and the nervous system in the gastrointestinal tract (enteric nervous system). Thus, it is unsurprising that gastrointestinal disorders, particularly constipation, diarrhoea and abdominal pain, are highly comorbid in individuals with ASD. Gastrointestinal problems have also been repeatedly associated with increased severity of the core symptoms diagnostic of ASD and other centrally mediated comorbid conditions, including psychiatric issues, irritability, rigid-compulsive behaviours and aggression. Despite the high prevalence of gastrointestinal dysfunction in ASD and its associated behavioural comorbidities, the specific links between these two conditions have not been clearly delineated, and current data linking ASD to gastrointestinal dysfunction have not been extensively reviewed. This Review outlines the established and emerging clinical and preclinical evidence that emphasizes the gut as a novel mechanistic and potential therapeutic target for individuals with ASD. Gastrointestinal issues are common in autism spectrum disorders (ASDs). This Review provides a comprehensive overview of the clinical and mechanistic connections between ASDs and gastrointestinal disorders and how these data might be utilized for future research and novel therapeutic targets. Autism spectrum disorders (ASDs) are a complex, diverse set of neurodevelopmental disorders accompanied by many psychiatric and peripheral comorbidities.Gastrointestinal issues, in particular, constipation, diarrhoea and abdominal pain, are among the most common comorbidities diagnosed in individuals with ASD.Observations from preclinical and clinical studies have highlighted the potential importance gut luminal factors, including the gut microbiota, its metabolites and/or other enteric neurotransmitters or modulators, in the pathophysiology of ASD.Genetic and/or environmental risk factors that affect central and enteric nervous system development and/or function have increasingly been revealed as causative factors underlying the pathogenesis and/or symptomology of co-occurring gastrointestinal problems in ASD.Some studies have shown that modulation of the gut microbiota or its metabolites might offer potential novel therapeutic options for treating specific phenotypes characteristic of ASD.