Despite the increase in the prevalence of autism spectrum disorder (ASD), currently, there are no treatments that can effectively reverse ASD core features. Thus, the development of new therapies and therapeutic strategies is of importance. In addition to the core ASD traits, many children also exhibit gastrointestinal comorbidities and changes in the populations of microbes inhabiting in their guts. Moreover, a correlation between the severity of the gastrointestinal distress and the severity of behavioral symptoms has been reported1. These results raise the intriguing possibility that gut-brain communication is dysfunctional in ASD and interventions that target the gastrointestinal tract may alleviate some of the behavioral changes associated with ASD.
Mauro Costa-Mattioli’s laboratory has previously demonstrated that treatment with a commensal bacterial species, Lactobacillus reuteri, rescued social deficits in genetic, environmental and idiopathic mouse models of ASD2,3, and they have begun to elucidate the mechanism through which this rescue occurs3,4.
In the current project, Costa-Mattioli’s team plans to examine whether both microbes and L. reuteri-induced metabolites could represent a promising and broadly effective translational therapy for neurodevelopmental conditions with social challenges. To test this hypothesis, they plan to use mouse and rat genetic models for ASD (all genes will be high-confidence ASD risk genes, as categorized by SFARI Gene). They plan to test whether these models exhibit changes in their microbiome composition and whether L. reuteri (and L. reuteri-induced metabolites) can rescue social deficits. Moreover, they plan to identify the molecular mechanisms through which this rescue occurs by using transcriptomics, metabolomics, pharmacology and genetics in both in vivo and in vitro systems.
The results of this project will strengthen our emerging and relatively unexplored understanding of how gut microbes control complex ASD-related behaviors and could advance the development of microbial-based non-invasive therapies for ASD.