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Defining the Underlying Biology of Gastrointestinal Dysfunction in Autism

2011 Suzanne and Bob Wright Trailblazer

University of California, Davis
Davis, California
United States


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.

Disseminations
TypeDateTitle/Link
Publication12/15/2012Levels of Soluble Platelet Endothelial Cell Adhesion Molecule-1 and P-Selectin Are Decreased in Children with Autism Spectrum Disorder
Publication10/11/2012Myeloid dendritic cells frequencies are increased in children with autism spectrum disorder and associated with amygdala volume and repetitive behaviors.
Publication10/04/2011The expression of caspases is enhanced in peripheral blood mononuclear cells of autism spectrum disorder patients.
Publication08/28/2011The role of immune dysfunction in the pathophysiology of autism
Publication08/23/2012Placental regulation of maternal-fetal interactions and brain development.
Publication08/17/2012Cytokine dysregulation in autism spectrum disorders (ASD): Possibnle role of the environment
Publication08/01/2013Antibodies against Food Antigens in Patients with autism spectrum disorders
Publication07/31/2012Modeling an autism risk factor in mice leads to permanent immune dysregulation
Publication07/25/2012Maternal immune activation causes age- and region-specific changes in brain cytokines in offspring throughout development
Publication06/19/2012Levels of Soluble Adhesion Molecules PECAM-1 and P-Selectin are Decreased in Children with Autism Spectrum Disorder
Publication05/01/2014Gastrointestinal problems in children with autism, developmental delays or typical development
Publication04/13/2013Cannabinoid Recepter Type 2, but not Type 1 is up-regulated in peripheral blood mononuclear cells of children affected by autistic disorders
Publication04/05/2013Zonulin as prehaptoglobin2 regulates lung permeability and activates the complement system
Publication03/20/2018Differential immune responses and microbiota profiles in children with autism spectrum disorders and co-morbid gastrointestinal symptoms
Publication02/02/2023Preliminary Findings of Elevated Inflammatory Plasma Cytokines in Children with Autism Who Have Co-Morbid Gastrointestinal Symptoms
Publication01/30/2012Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism

Status:

Completed

Investigator:

Ashwood, Paul

Grant Term:

2 years

Award Type:

Suzanne and Bob Wright Trailblazer

Grant Amount:

$769,942.80

Institution Website:

http://www.ucdavis.edu

Grant ID:

7567