Speakers
Description
Chronic inflammatory disorders, such as inflammatory bowel disease (IBD), are characterized by unpredictable transitions between disease remission and debilitating flare-ups driven by gut dysbiosis. Despite extensive research, the mechanistic drivers of these relapse-remission cycles and the optimal strategies to restore stability remain elusive. Here, we introduce a minimal mechanistic ordinary differential equation model coupling bacterial burden and innate immune activity, which we calibrated to longitudinal in vivo infection data and validated against an independent chemically induced colitis dataset. Using steady-state control maps, we delineate distinct disease regimes and demonstrate that increasing immune recruitment capacity can shift flare-prone dynamics into a stable recovery state. To operationalize this finding, we applied Computational Singular Perturbation (CSP) to dissect the multi-scale dynamics of the system, pinpointing a critical "explosive" time window preceding flare peaks. CSP diagnostics identified immune decay as the dominant driver of oscillation growth, enabling the design of a time-adaptive, threshold-triggered intervention protocol that systematically suppresses recurrent flares. Ultimately, this analysis challenges the strictly immunosuppressive paradigm of current therapies, providing a mathematically grounded framework for stabilizing dysbiosis through targeted immune augmentation.
