Abstract
Autism spectrum disorder (ASD) is a range of neurodevelopmental conditions that are sharply increasing in prevalence worldwide. Intriguingly, ASD is often accompanied by an array of systemic aberrations including (1) increased serotonin, (2) various modes of gastrointestinal disorders, and (3) inflammatory bowel disease (IBD), albeit the underlying cause for such comorbidities remains uncertain. Also, accumulating number of studies report that the gut microbial composition is significantly altered in children with ASD or patients with IBD. Surprisingly, when we analyzed the gut microbiota of poly I:C and VPA-induced mouse models of ASD, we found a distinct pattern of microbial dysbiosis that highly recapitulated those reported in clinical cases of ASD and IBD. Moreover, we report that such microbial dysbiosis led to notable perturbations in microbial metabolic pathways that are known to negatively affect the host, especially with regards to the pathogenesis of ASD and IBD. Lastly, we found that serum level of serotonin is significantly increased in both poly I:C and VPA mice, and that it correlates with increases of a bacterial genus and a metabolic pathway that are implicated in stimulation of host serotonin production. Our results using animal model identify prenatal environmental risk factors of autism as possible causative agents of IBD-related gut microbial dysbiosis in ASD, and suggest a multifaceted role of gut microbiota in the systemic pathogenesis of ASD and hyperserotonemia.
Highlights
Autism spectrum disorder (ASD) is characterized by core deficits in neurodevelopmental milestones
When we analyzed the serum from ASD mice, we observed a significant increase of serum serotonin level compared to CTL mice (Fig. 4c), a phenomenon not previously reported in polycytidylic acid (poly I):C and valproic acid (VPA) mice models of ASD
Children with ASD are commonly burdened with various gastrointestinal (GI) disorders [4] ranging from mild GI discomfort and constipation [49] to inflammatory bowel disease (IBD)
Summary
Autism spectrum disorder (ASD) is characterized by core deficits in neurodevelopmental milestones. A majority of children with ASD suffer from a wide range of systemic aberrations such as increased serum serotonin (40% prevalence) [1,2,3], gastrointestinal (GI) distress (up to 90%) [4], and inflammatory bowel disease (IBD) [5]. One of the most directly affected host site by microbial dysbiosis is the GI tract, Co-occurrence of two or more mutually exclusive, etiologically unrelated diseases is rare; the fact that GI disorders and IBD are so prevalent among children with ASD is highly suggestive of a common cause for the behavioral abnormalities and systemic aberrations in ASD. Accumulating number of studies report that the gut microbial composition and several microbial metabolic pathways are significantly altered in children with ASD [12, 13] as well as patients with IBD [14, 15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
