A Pilot Study of Microbiome in Patients With Autism Spectrum Disorder and Their Unaffected Siblings
Condition: Autism Spectrum Disorder
MeSH terms: Autistic Disorder; Autism Spectrum Disorder; Child Development Disorders, Pervasive
Study type: Observational

Summary: 
      The primary aims are to identify important gut microbiota signatures for youth with ASD, to
      identify dysbiosis features for different levels of ASD features and clinical courses, to
      search the possibility to intervene the disease course if we can tease out the dysbiosis
      responsible for the flare-up and improvement of the symptoms of the disease. The secondary
      aims are to identify the clinical and neuropsychological measures that are associated with
      direct and indirect regulation or interactions from gut-brain axis signaling, and based our
      preliminary results on reducing the measures for future large-scale microbiome study in ASD.
    

Detailed description: 
      Background: Despite increased public awareness of autism spectrum d isorder (ASD) and
      extensive research on this neurodevelopmental disorder in the past decades, the underlying
      mechanisms of ASD remain unclear, and ASD is still recognized as having the highest disease
      and care burden among child psychiatric disorders regarding its long-term impairment across
      the lifespan. Hence, identifying the biomarkers for early detection and effective biological
      treatments for ASD is among the most challenging tasks all over the world. The concerns about
      physical comorbidities such as immune dysregulation, allergy, and gastrointestinal issues,
      etc. emerged in the recent decade. Hence, the new perspective of searching for the underlying
      mechanism for ASD also targets the associations between microbiota and ASD. However, despite
      many microbiome studies in ASD, they provided limited knowledge about the specific link that
      particular imbalance gut bacteria could affect the behavioral deficits in ASD because lack of
      consideration of the clinical and genetic heterogeneity of ASD. With only a few studies
      examining the well-defined ASD-related impairments, the GI system dysfunction, and the
      microbiomes, the associations among ASD-related symptoms, GI symptoms, and microbiota remain
      indistinct. Therefore, the investigators propose this pilot study to fill the gap between the
      potential role of microbiome as a biomarker for ASD to facilitate developing the treatment
      for ASD.

      Method and material: The case-sibling control study design will be used to investigate
      microbiome in 60 probands with ASD, aged 7-25 yrs old, and 30 unaffected siblings either from
      the PI Gau's ASD cohort or the Department of Psychiatry, National Taiwan University Hospital.
      The parents of all the subjects will receive the Autism Diagnostic Interview-Revised (ADI-R)
      interviews and report on the questionnaires regarding autistic symptoms, emotional/behavioral
      problems, social functions, G-I symptoms, and life quality. The ASD and sibling subjects will
      receive the Autism Diagnostic Observation Scale and neuropsychological tasks. The experiment
      of microbiome will be conducted by the core lab of microbiome (co-PI Ni) at the college of
      medicine, National Taiwan University. The data analyses will combine microbiomics and the
      extensive behaviors/cognitive function variables to establish an objective potential
      pipeline.

      Anticipated outcome: With the accomplishment of this project, the investigators will
      establish the comprehensive yet fewer bios for the ASD risk bio-factors in Asia, and provide
      the potential clinical interview and assessments related to GI symptoms regulated by
      microbiota. The potential biomarkers may be further used to developing the treatment for ASD.

      Significance: Several features of this project constitute its significance: a wealth of
      measures of ASD phenotypes (valid phenotype), ASD as a catastrophic disease (importance), the
      first ASD study with unaffected sibling design for microbiomics studies in ASD (originality),
      and new approaches and technologies (novelty) for searching microbiomics in ASD.
    

Intervention name(s): Psychiatric diagnosis; ASD diagnosis
Intervention type(s): Other; Other
Intervention description(s): Kiddie Schedule for Affective Disorders & Schizophrenia (K-SADS) for DSM-5; Autism Diagnostic Interview-revised (ADI-R) and Autism Diagnostic Observation Scale (ADOS)
Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        The cohort was established at the Department of Psychiatry, National Taiwan University
        Hospital (NTUH) starting from 2007.
      
Biospecimen description: 
      5 g of stool sample