Defining the Underlying Biology of Gastrointestinal Dysfunction in Autism
University of California, Davis
Suzanne and Bob Wright Trailblazer
Autism Spectrum Disorders (ASD) are behaviorally defined by impairments in communication, social interactions, and repetitive stereotypic behaviors. Many children with ASD also experience gastrointestinal (GI) symptoms such as irregular bowel movements. A number of studies have described the presence of GI inflammation and altered immune function in children with ASD and GI symptoms. In these children the presence of GI symptoms is often associated with increased irritability, tantrums, aggressive behavior, and sleep disturbance. In known diseases that affect the gut such as celiac disease, changes in behavior are also seen and support a link between GI function/symptoms and behavioral changes in ASD. There is also evidence that the bacteria within the gut of children with ASD are different relative to typically developing children. Elimination of these gut bacteria with antibiotics in some individuals can lead to a temporary improvement in some behavioral symptoms. In addition, based on beneficial reports on behaviors and GI symptoms, dietary interventions are commonly used in ASD. These diets may change bacterial composition and also remove substances that could provoke GI inflammation. Collectively, these findings suggest that GI symptoms may define a unique subgroup of individuals with ASD. The connections between irregular bowel movements, gut barrier function, gut bacteria, immune function, and abnormal behavior have as yet not been investigated in ASD. The proposed studies aim to examine these potential links. In the same children with ASD, with and without irregular bowel movements, the investigators will examine the relationships between gut bacteria, immune profiles, and the function of epithelial cells that line the gut and provide a barrier with the environment. Using a validated animal model of autistic features, they explore the mechanisms of altered GI function, barrier function and its relationship to immune activation and ASD-like behaviors, as well as the potential of novel probiotic therapeutic approaches to restore barrier function and ameliorate GI symptoms, immune activation and abnormal behavior. This study will provide critical information on the irregular bowel habits in ASD, a problem that affects a significant number of children with ASD.