Role of the microbiome in diabetic wound healing: implications for new therapeutic approaches

Diabetic wounds present a persistent clinical challenge due to delayed healing and an increased risk of infection and complications. The rising global prevalence of diabetes and the associated burden of chronic, non-healing wounds highlight the urgent need for innovative and effective therapeutic strategies. Recent research has underscored the critical yet often overlooked role of the skin microbiome in modulating wound healing outcomes. This review explores the complex interactions between the skin microbiome and diabetic wound healing, aiming to inform the development of microbiome-based interventions. The review begins by outlining the composition and physiological functions of the skin microbiome, emphasizing its roles in maintaining cutaneous homeostasis, immune regulation, and barrier integrity. It then examines how diabetes-induced hyperglycemia disrupts microbial balance, leading to dysbiosis, impaired immune responses, and increased colonization by opportunistic pathogens. These alterations contribute to the formation of persistent biofilms, chronic inflammation, impaired angiogenesis, and ultimately, delayed wound repair. Mechanisms by which the microbiome exacerbates wound pathology are discussed, alongside emerging therapeutic strategies targeting the wound microbiota. These include probiotics, prebiotics, bacteriophage therapy, antimicrobial peptides, and microbiome-responsive dressings. Innovative approaches such as photoimmuno-antimicrobial therapies and advanced drug delivery systems are also considered for their potential to enhance treatment efficacy. Despite these promising developments, significant challenges remain in deciphering the full complexity of microbiome-host interactions and translating this knowledge into clinical practice. The review emphasizes the future potential of personalized, microbiome-based therapies tailored to individual microbial profiles and advocates for a precision medicine approach to diabetic wound care. Additionally, it highlights the need for further research into non-bacterial components of the microbiome and the integration of multi-omics technologies with advanced wound management strategies.