Enhanced Statistical Analysis of Phase 1 FMT Trial Crestovo Master Research Agreement: Research Plan 1: Project: Enhanced statistical analysis of Phase 1 FMT trial Metagenomics analysis and enhanced multi-omics/statistical analysis of Phase 1 FMT Trial GOAL: The overarching goal is to define specific microbes/metabolites as therapeutic targets both for treatment of ASD and biomarkers for diagnosis of ASD. SUMMARY: We propose to obtain shotgun sequencing data to perform metagenomics analysis on milestone samples (Baseline and the end of 8-weeks treatment). Shotgun metagenomics datasets will allow us to identify microbial pathways that could potentially explain improvements in GI and ASD symptoms after the FMT trial. We previously obtained fecal and blood metabolomics and 16S rRNA gene sequencing datasets of the Phase 1 FMT trial. By integrating those results with the metagenomics analysis, we will be able to test specific hypotheses for the role of the gut microbiome in ASD GI and behavioral symptoms and generate additional hypotheses for the same. SPECIFIC OBJECTIVES: By performing metagenomics sequencing and analysis, we will be able to: 1) Test whether specific pathways, including neurotransmitter biosynthesis and phenol production through aromatic amino acid metabolism, are at higher abundances in samples from ASD participants compared to neurotypical participants. 2) Determine the species identity of the Prevotella strain(s), which were found to have a decreased relative abundance in ASD samples compared to neurotypical samples 3) Design and perform other exploratory analyses to generate and test hypotheses on how microbial metabolites and pathways may link GI and ASD behavioral symptoms, as well as how FMT can ameliorate both GI and ASD symptoms. Results from exploratory work may also lead to a better understanding of how to isolate and culture some members of the gut microbial community. IMPACT: The metagenomics analysis will be a bridge to connect our current knowledge based on two existing datasets: 16S rRNA gene sequencing data (microbial profiles) and fecal and blood metabolomics (metabolite profiles). By integrating these multi-omic datasets, we will have a more comprehensive understanding how gut microbes contribute to the improvement in GI and ASD symptoms that we observed in Phase 1 FMT trial. Metagenomics sequencing and analysis will also provide deeper understanding of the microbial community changes during the trial and will enhance isolation efforts.
|Effective start/end date||3/1/18 → 9/30/20|
- INDUSTRY: Domestic Company: $219,417.00
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