Skin Microbiota and its Interplay with Wound Healing

Marjana Tomic-Canic, Jamie L Burgess, Katelyn E O'Neill, Natasa Strbo, Irena Pastar, Marjana Tomic-Canic, Jamie L Burgess, Katelyn E O'Neill, Natasa Strbo, Irena Pastar

Abstract

The skin microbiota is intimately coupled with cutaneous health and disease. Interactions between commensal microbiota and the multiple cell types involved in cutaneous wound healing regulate the immune response and promote barrier restoration. This dialog between host cells and the microbiome is dysregulated in chronic wounds. In this review, we first describe how advances in sequencing approaches and analysis have been used to study the chronic wound microbiota, and how these findings underscored the complexity of microbial communities and their association with clinical outcomes in patients with chronic wound disorders. We also discuss the mechanistic insights gathered from multiple animal models of polymicrobial wound infections. In addition to the well-described role of bacteria residing in polymicrobial biofilms, we also discuss the role of the intracellular bacterial niche in wound healing. We describe how, in contrast to pathogenic species capable of subverting skin immunity, commensals are essential for the regulation of the cutaneous immune system and provide protection from intracellular pathogens through modulation of the antimicrobial molecule, Perforin-2. Despite recent advances, more research is needed to shed light on host-microbiome crosstalk in both healing and nonhealing chronic wounds to appropriately guide therapeutic developments.

Conflict of interest statement

Marjana Tomic-Canic, Jamie L. Burgess, Katelyn E. O’Neill, Natasa Strbo, and Irena Pastar have no conflicts of interest that are directly relevant to the content of this article.

Figures

Fig. 1
Fig. 1
Cutaneous wound healing progression: overlapping phases of acute healing. Epidermal keratinocytes, neutrophils, and macrophages are major cell types involved in the inflammatory response that occurs concurrently with hemostasis in the early stages of wound healing. Colonization of wounds with commensal microbiota may promote wound healing through activation of the innate immune response. In the proliferation phase, keratinocytes multiply and migrate, fibroblasts migrate and deposit extracellular matrix, and angiogenesis occurs. Extracellular matrix remodeling results in scar formation and the ultimate restoration of the skin barrier. The most common growth factors and cytokines are shown. EGF epidermal growth factor, IL interleukin, TGFβ transforming growth factor-beta, TNFα tumor necrosis factor-alpha, VEGF vascular endothelial growth factor
Fig. 2
Fig. 2
Cutaneous immunity is differentially regulated by commensal and pathogenic microorganisms through modulation of Perforin-2. a Colonization of the wound with commensal bacteria may promote wound healing by inducing antimicrobial proteins such as Perforin-2, thus stimulating a protective immune response against pathogenic bacteria. b Wound infection with pathogenic bacteria results in Perforin-2 suppression in both hematopoietic and nonhematopoietic cells and inhibition of healing

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