The Gut Microbiota and Autism Spectrum Disorders

Gastrointestinal (GI) symptoms are a common comorbidity in patients with autism spectrum disorder (ASD), but the underlying mechanisms are unknown. Many studies have shown alterations in the composition of the fecal flora and metabolic products of the gut microbiome in patients with ASD. The gut microbiota influences brain development and behaviors through the neuroendocrine, neuroimmune and autonomic nervous systems. In addition, an abnormal gut microbiota is associated with several diseases, such as inflammatory bowel disease (IBD), ASD and mood disorders. Here, we review the bidirectional interactions between the central nervous system and the gastrointestinal tract (brain-gut axis) and the role of the gut microbiota in the central nervous system (CNS) and ASD. Microbiome-mediated therapies might be a safe and effective treatment for ASD. Autism spectrum disorder (ASD) constitutes a group of brain developmental disorders, and it is defined by stereotyped behavior and deficits in communication and social interaction. ASD has a significant influence on the development of children and on society. In 2012, the estimated prevalence of ASD was 14.6 per 1,000 children aged 8 years, and the prevalence was significantly higher in boys (23.6 per 1,000) than that in girls (5.3 per 1,000) (Christensen et al., 2016). The cost of caring for a child with ASD but without an intellectual disability is £0.92 million in the United Kingdom and $1.4 million in the United States. The main costs associated with the care of children with ASD are special education services and a loss of parental productivity (Buescher et al., 2014). Therefore, the economic effects of ASD have prompted researchers to search for effective interventions. However, identifying the exact etiology and pathology of ASD is difficult, and available effective therapies are limited (Rossignol and Frye, 2012). Previous studies have focused on genetic causes, dysregulation of the immune system, inflammation, exposure to environmental toxicants, and the gut microbiota (Fakhoury, 2015). The heritability of ASD and autistic disorder was approximately 50% among Swedish children, suggesting that both genetic and environmental factors play important roles in the development of ASD (Hallmayer et al., 2011; Sandin et al., 2014). Accumulating evidence demonstrates that gastrointestinal (GI) symptoms, such as abdominal pain, gaseousness, diarrhea, constipation and flatulence, are a common comorbidity in patients with ASD (Chaidez et al., 2014). A study by Gorrindo et al. identified constipation as the most common symptom (85%) in children with ASD according to parental reports and evaluations by pediatric gastroenterologists (Gorrindo et al., 2012). The prevalence of GI symptoms ranges from 23 to 70% in children with ASD (Chaidez et al., 2014). Furthermore, the observed GI symptoms are associated with the severity of ASD (Adams et al., 2011; Gorrindo et al., 2012). Although these studies did not show a cause-effect relationship between GI symptoms and ASD, the findings suggest that the gut plays an important role in the etiology of ASD. The gut consists of millions of microbiota, and we hypothesize that the microbiota and its metabolites might be involved in the pathophysiology of ASD. Several articles have reviewed the influence of the gut microbiota on the animal central nervous system (CNS) and suggested the existence of a microbiota gut-brain axis (Bienenstock et al., 2015; Mayer et al., 2015). The microbiota-gut-brain axis is likely the method of communication between the brain and the gut microbiota. This article reviews the role of the gut microbiota in the pathology of ASD. Strategies that modulate the gut microbiota might constitute a potential therapy for patients with ASD