Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental condition manifesting with impaired social interaction and communication, and restricted and repetitive behaviors and interests. In this perspective article, a more comprehensive approach than the gut-brain axis, hereby termed the "gut-immune-endocrine-brain" axis, is taken, based on which a personalized treatment plan for ASD is presented. ASD has no known etiology or cure, making desperate parents willing to try any treatment that worked for an individual with ASD, without much regard for its effectiveness, safety or side effects. This has been the case for restrictive dietary interventions as gluten-free/casein-free and ketogenic diets and recently, probiotics have emerged as the new such fad. One of the concerns about these dietary and probiotic treatments is their non-specificity: they may not be effective for all individuals with ASD, not all probiotic strains may have the beneficial qualities advertised indiscriminately for probiotics, and strains conferring benefits in one condition may not be probiotic in another. Not all children with ASD show immune reactivity to dietary proteins in wheat and milk, and wheat and milk may not be the only dietary elements to which reactivity is exhibited, where dietary aquaporins that resemble human aquaporins may elicit antibody reactivity in genetically susceptible individuals, which may include individuals with ASD. These observations are utilized to formulate a three-step plan to create effective, targeted, personalized treatments with as few side effects as possible, enabled by a systems approach connecting the various findings for dietary, immune, and neuroautoimmune reactivity in individuals with ASD.