Regenerative Microbiology: Harnessing Bacterial Antagonism and Spatiotemporal Signaling for Diabetic Wound Repair

Abstract

Chronic diabetic foot ulcers represent a persistent clinical challenge characterized by a “locked” inflammatory phase, biofilm‐mediated infection, and impaired tissue regeneration. Because conventional antibiotic and debridement therapies fail to resolve dysbiosis or stimulate healing, microbial antagonism has emerged as a potent biological principle for wound restoration. This narrative review integrates ecological evidence and mechanistic insights from animal models and early human studies to explore how beneficial microorganisms, including probiotics, bacteriophages, and competitive consortia, actively reshape diabetic wound environments. We examined the multifaceted mechanisms of these interactions, ranging from direct pathogen inhibition to host immunomodulation and metabolic signaling via conserved pathways such as the p40/epidermal growth factor receptor (EGFR)/PI3K axis. To address significant translational barriers, we introduce a “Regenerative Microbiology” framework that emphasizes spatiotemporal coordination and precision stratification. By tailoring the use of live biotherapeutics or metabolically independent postbiotics to a patient's vascular and microbial profiles, this approach offers a strategic roadmap for transforming the management of infection‐driven tissue damage in chronic diseases.