A product of skin microbiota improves hallmarks of wound healing in diabetes mellitus: an in vitro investigation

Sabir, Aveen

Abstract

Diabetes mellitus is a critical global health disease characterised by persistent hyperglycaemia, which leads to various complications. Poor wound healing and diabetic foot ulcers are the two main complications of this disease. Lysates and cellfree supernatants prepared from some Lactobacillus spp. were found to improve the hallmarks of wound healing under healthy conditions in vitro. Dysbiosis in the skin microbiota is widely reported in the skin of diabetic patients, and the presence of some members of the skin microbiota was correlated with a positive prognosis of diabetic foot ulcers. Thus, the present study aimed to test the effects of lysates or cell-free supernatants prepared from some members of the skin microbiota on wound healing in diabetes mellitus in vitro. Bacterial lysates and cell-free supernatants were prepared from three main commensal skin bacteria: Staphylococcus epidermidis, Staphylococcus aureus, and Corynebacterium jeikeium. Human skin cells, particularly human skin fibroblasts and keratinocytes, were co-cultured with the skin commensal lysate and cell-free supernatant in euglycemic and hyperglycaemic glucose concentrations. Various in vitro experiments were performed: proliferation assay (MTS assay), migration assay (scratch assay), and transcriptomic analysis (whole mRNA sequencing). Only one bacterial product, Staphylococcus epidermidis lysate, significantly induced the proliferation and migration of human skin fibroblasts at hyperglycaemic glucose concentrations. Transcriptomic analysis revealed that the main effect of Staphylococcus epidermidis lysate on fibroblasts was through the significant enrichment of the IL-17 signalling pathway. Moreover, CXCL6 was the main chemokine that was significantly upregulated and secreted by fibroblasts when exposed to Staphylococcus epidermidis lysate at hyperglycaemic glucose concentrations. These results indicate that the Staphylococcus epidermidis lysate improves the hallmarks of wound healing under hyperglycaemic conditions in vitro. Moreover, these findings encourage further ex vivo, in vivo, and clinical studies to investigate the efficacy and safety of Staphylococcus epidermidis lysate as a novel therapeutic for the treatment of diabetic foot ulcers.

• Thesis Type: Thesis
• Acceptance Date: Mar 24, 2025
• Online Publication Date: Mar 27, 2025
• Deposit Date: Mar 24, 2025
• Publicly Available Date: Apr 28, 2025
• Award Date: Mar 27, 2025