Reprogramming chronic wounds: the emerging role of microbiome-targeted therapies in diabetic foot ulcers

Diabetic foot ulcers (DFUs) represent one of the most severe complications of diabetes mellitus, frequently leading to chronic infection, delayed wound healing, and lower-limb amputations. Despite advances in wound care, current therapeutic strategies largely rely on broad-spectrum antibiotics and mechanical interventions, which often fail to address the complex biological environment of non-healing wounds. Emerging evidence indicates that DFUs are strongly associated with alterations in the wound microbiome, including microbial dysbiosis, polymicrobial biofilm formation, and persistent inflammatory responses. These factors collectively contribute to impaired tissue regeneration and resistance to conventional therapies. Consequently, microbiome-targeted therapeutic strategies are gaining increasing attention as a promising approach for DFU management. Novel interventions such as bacteriophage therapy, probiotic and postbiotic-based wound dressings, and CRISPR-mediated genome editing provide precise tools for disrupting pathogenic biofilms, attenuating microbial virulence, and overcoming antimicrobial resistance while preserving beneficial microbial communities. In parallel, advances in rapid microbiome diagnostics, smart wound dressings, nanotechnology-based drug delivery systems, and data-driven personalized treatment platforms are enabling more adaptive and targeted wound management. By shifting the perspective from treating DFUs as simple infections to understanding them as complex microbial ecosystems, these emerging strategies offer new opportunities to enhance healing outcomes.