Gastrointestinal symptoms and autism spectrum disorder: links and risks - a possible new overlap syndrome.

Autism spectrum disorder (ASD) is a genetically determined neurodevelopmental brain disorder presenting with restricted, repetitive patterns of behaviors, interests, and activities, or persistent deficits in social communication and social interaction. ASD is characterized by many different clinical endophenotypes and is potentially linked with certain comorbidities. According to current recommendations, children with ASD are at risk of having alimentary tract disorders - mainly, they are at a greater risk of general gastrointestinal (GI) concerns, constipation, diarrhea, and abdominal pain. GI symptoms may overlap with ASD core symptoms through different mechanisms. These mechanisms include multilevel pathways in the gut-brain axis contributing to alterations in behavior and cognition. Shared pathogenetic factors and pathophysiological mechanisms possibly linking ASD and GI disturbances, as shown by most recent studies, include intestinal inflammation with or without autoimmunity, immunoglobulin E-mediated and/or cell-mediated GI food allergies as well as gluten-related disorders (celiac disease, wheat allergy, non-celiac gluten sensitivity), visceral hypersensitivity linked with functional abdominal pain, and dysautonomia linked with GI dysmotility and gastroesophageal reflux. Dysregulation of the gut microbiome has also been shown to be involved in modulating GI functions with the ability to affect intestinal permeability, mucosal immune function, and intestinal motility and sensitivity. Metabolic activity of the microbiome and dietary components are currently suspected to be associated with alterations in behavior and cognition also in patients with other neurodegenerative diseases. All the above-listed GI factors may contribute to brain dysfunction and neuroinflammation depending upon an individual patient's genetic vulnerability. Due to a possible clinical endophenotype presenting as comorbidity of ASD and GI disorders, we propose treating this situation as an "overlap syndrome". Practical use of the concept of an overlap syndrome of ASD and GI disorders may help in identifying those children with ASD who suffer from an alimentary tract disease. Unexplained worsening of nonverbal behaviors (agitation, anxiety, aggression, self-injury, sleep deprivation) should alert professionals about this possibility. This may shorten the time to diagnosis and treatment commencement, and thereby alleviate both GI and ASD symptoms through reducing pain, stress, or discomfort. Furthermore, this may also protect children against unnecessary dietary experiments and restrictions that have no medical indications. A personalized approach to each patient is necessary. Our understanding of ASDs has come a long way, but further studies and more systematic research are warranted.