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Itarget-Autism Initiative: A Guiding Look into the Microbiome Profile in Autism Spectrum Disorders
Autism Spectrum Disorders (ASD) are complex neurodevelopmental conditions comprised of deficits in communication, social reciprocity and patterns of restrictive behaviours with preservative interests. Along with behavioural manifestations, individuals with ASD frequently report gastrointestinal disturbances. The iTARGET Autism Initiative (http://www.itargetautism.ca/) is a collaborative initiative which aims to identify children with or at risk for ASDs and provide a framework to classify patients based on genotype and deep-phenotype (clinome, metabolome, proteome, gut microbiome) profiles.
Objectives: To determine the role of the microbiome on ASD through the gut-brain axis. The central hypothesis surrounding the gut-brain axis, in regards to autism, is that ASD behaviours can be impacted by the microbiome and their metabolites which may cross the blood-brain barrier. Our analysis endeavours to identify these microbes and their metabolites.
Methods: We recruited 39 ASD affected subjects both with and without gastrointestinal symptoms. These patients will undergo WGS analysis in addition to microbiome, metabolome and proteome analysis. A control fecal sample is collected for each patient and is provided by either a sibling or same-sex parent. All collections are done through MolecularYou (https://molecularyou.com/), a Vancouver based company. 131 serum metabolites, 137 serum proteins and 73 urine metabolites have been analyzed in each affected subject. Serum and urine metabolome and proteome analysis is facilitated through MolecularYou’s affiliates, The Metabolomics Innovation Centre (TMIC; https://www.metabolomicscentre.ca/) and The British Columbia Proteomics Network (BCPN; http://bcpn.ca/). The microbiome is analysed by MolecularYou affiliate, Microbiome Insights (https://microbiomeinsights.com/). The microbiome analysis consists of 16S rDNA amplicon sequencing via the Illumina MiSeq platform to determine diversity and abundance of microbial species and shotgun metagenome sequencing to identify errors in metabolism within the microbiota.
Results: Analysis of these data from 39 ASD affected subjects is currently underway. Using the same methods, we have preliminary results from five ASD affected patients, two with available control data. Our analysis has suggested that there may be an altered microbiome profile in ASD affected individuals specifically involving the Bacteroidetes and Firmicutes species. Each of the five affected patients was found to have Bacteroidetes abundance at increased levels and Firmicutes abundance at decreased levels. Three of these subjects reported gastrointestinal symptoms, while the remaining two did not. The subjects with the most altered microbiome profile also were those with the most severe behavioural manifestations of ASD.
Conclusions: Despite the small sample size, we see promising trends consistent with the literature that there is an altered microbiome profile present in individuals with ASD. These findings act as a guide for what we might expect to find following the completed analysis of our cohort. If the unique microbiome profile reaches statistical significance in association with autism and/or its symptoms, this may have implications in regards to specific diagnostic testing, management and prevention.