STRIKE-T2D: Identifying Causal Microbial Strains Underlying Type 2 Diabetes via Longitudinal Analysis

Objective

STRIKE-T2D (Strain-level Interpretation of Key Effectors in Type 2 Diabetes) aims to uncover specific gut microbial strains that causally influence the progression of type 2 diabetes (T2D). While many human studies have linked microbiome changes to metabolic disease, most remain observational and lack the resolution to identify microbial drivers rather than bystanders. This project integrates a longitudinal, genetically controlled fecal microbiota transplantation (FMT) mouse model with strain-resolved metagenomics and multi-omics analysis. Using prediabetic donors from a well-characterized cohort (IGT), germ-free mice will be colonized and phenotyped over time to track microbiota-driven metabolic changes. High-resolution metagenomic workflows will enable reconstruction and tracking of microbial strains and genetic variants linked to host glycemic outcomes. Beyond association, STRIKE-T2D will apply causal mediation models to link microbial features with intermediate metabolic traits, and experimentally validate prioritized candidates both in vivo and in vitro. Ultimately, the project will identify microbial strains and functions that reproducibly alter host glucose metabolism—offering new insights into disease pathogenesis and pointing toward future diagnostic or therapeutic strategies.