Type 2 diabetes (T2D) is characterized by substantial inter-individual heterogeneity in glycemic regulation and responses to dietary and therapeutic interventions. Growing evidence suggests that the gut microbiome contributes to this heterogeneity, yet it remains unclear how microbiome–diet interactions shape dynamic glycemic regulation during disease progression and determine individual responses to interventions. The Personalized Responses to Interventions Stratified by gut Microbiome in T2D (PRISM) project aims to identify gut microbial signatures associated with dynamic glucose homeostasis and predictive of individualized responses to dietary and probiotic interventions. The project integrates continuous glucose monitoring (CGM), gut metagenomics, clinical phenotyping, dietary information, and other multi-omics data from deeply phenotyped longitudinal cohorts and controlled intervention studies. First, high-resolution CGM data will be processed to characterize daily glycemic variability and postprandial glucose responses. These phenotypes will be integrated with gut metagenomic profiles to identify microbial species and functional pathways associated with dynamic glycemic regulation and subsequent glycemic deterioration. Second, candidate microbial signatures will be evaluated for their ability to predict individualized postprandial glycemic responses to standardized meals with different dietary compositions, allowing the identification of both shared and meal-specific microbial predictors. Third, microbial signatures associated with responsiveness to next-generation probiotic treatment will be investigated and compared with dietary-response signatures to identify common and context-specific determinants of metabolic responsiveness. Statistical modelling and machine-learning approaches will be used to integrate high-dimensional microbiome, CGM, clinical, and multi-omics datasets, with rigorous cross-validation and independent validation where applicable. By combining longitudinal observational data with controlled dietary and probiotic interventions, PRISM aims to establish a robust framework for microbiome-informed precision nutrition and to identify predictive biomarkers that can support personalized strategies for T2D prevention and management.