Abstract
Diabetic foot syndrome (DFS) is a severe complication affecting millions of people worldwide, yet its clinical management remains predominantly reactive, focusing on established ulcers rather than early preventive measures. Although the role of the cutaneous microbiome in chronic wounds is recognized, longitudinal ecological shifts in the skin of the foot throughout the progression of diabetes mellitus remain underexplored. This structured narrative review evaluates transitional microbial dynamics from intact skin through to active ulceration and explores emerging microbiome-targeted therapies. Based on a structured literature search of PubMed, Scopus, and Web of Science, complemented by citation searching, and a narrative synthesis of 32 selected publications, current evidence suggests that diabetes-associated changes in the cutaneous microbiome involve heterogeneous alterations in microbial diversity and composition, which vary according to microbial community, anatomical location, and clinical status. DFS progression involves a profound ecological collapse, characterized by depletion of protective commensals (e.g., Staphylococcus epidermidis) and the predominance of virulent Staphylococcus aureus lineages alongside Gram-negative anaerobes. Consequently, precision interventions such as topical probiotics, synbiotics, and bacteriophage therapy have substantial potential to disrupt recalcitrant biofilms and reprogram host immunity toward pro-regenerative phenotypes. Ultimately, recognizing the skin as a primary target organ in diabetes mellitus highlights the need to shift DFS management toward a proactive framework. Validating these microbiome-modulating therapies through standardized clinical trials is crucial to restoring host-microbiota symbiosis and ultimately preventing lower-extremity amputations.