ena-STUDY-SNU-28-06-2016-15:13:26:956-589
Clinically-relevant gut microbial dysbiosis and hyperserotonemia in two mouse models of autism
Autism spectrum disorder (ASD) is often accompanied by comorbidities such as increased serotonin, gastrointestinal disorders, and inflammatory bowel disease (IBD), albeit the underlying cause for such comorbidities remains uncertain. We report that maternal injection of poly I:C and VPA results in a distinct pattern of microbial dysbiosis in the offspring that highly recapitulates those reported in clinical cases of ASD and IBD. Such microbial dysbiosis resulted in notable perturbations in metabolic pathways that may negatively affect the host. Lastly, serum level of serotonin was significantly increased as well, and it was accompanied by an increase in a bacterial genus and a metabolic pathway that have been implicated in the stimulation of host serotonin production. Our results 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.
Autism spectrum disorder (ASD) is often accompanied by comorbidities such as increased serotonin, gastrointestinal disorders, and inflammatory bowel disease (IBD), albeit the underlying cause for such comorbidities remains uncertain. We report that maternal injection of poly I:C and VPA results in a distinct pattern of microbial dysbiosis in the offspring that highly recapitulates those reported in clinical cases of ASD and IBD. Such microbial dysbiosis resulted in notable perturbations in metabolic pathways that may negatively affect the host. Lastly, serum level of serotonin was significantly increased as well, and it was accompanied by an increase in a bacterial genus and a metabolic pathway that have been implicated in the stimulation of host serotonin production. Our results 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.