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REVIEW ARTICLE

Skin Microbiota and its Interplay with Wound Healing Marjana Tomic‑Canic1 · Jamie L. Burgess1 · Katelyn E. O’Neill2 · Natasa Strbo2 · Irena Pastar1 

© The Author(s) 2020

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.

Key Points 

1 Introduction

A complex microbiome is a hallmark of chronic nonhealing wounds.

Chronic wounds, the most common of which are diabetic foot ulcers, pressure ulcers, venous leg ulcers, and nonhealing surgical wounds, are a major healthcare problem. Chronic wounds usually occur in older individuals with underlying conditions such as diabetes mellitus, vascular disease, and obesity [1]. Compromised immune and nutritional status, and chronic mechanical stress have also been shown to contribute to poor wound healing [2, 3]. Chronic wounds are associated with alarmingly high mortality: the 5-year mortality rates of ischemic (55%), neuropathic (45%), and neuroischemic (18%) diabetic foot ulcers [4] are higher than or similar to those associated with breast cancer and prostate cancer (18% and 8%, respectively) [5]. Chronic wounds are also associated with high healthcare costs: in the USA, total spending estimates for chronic nonhealing wounds ranged from US$28.1 to US$96.8 billion in 2014 according to a retrospective analysis of the Medicare 5% Limited Data Set [6]. Despite the alarming prevalence and high costs of care, efficient treatments are still lacking [2]. Cutaneous wound healing is a complex and very organized process, tightly controlled by several cell types through the secretion of growth factors, cytokines, and chemokines as illustrated in Fig.  1 [2]. Disruption of this process

Pathogenic bacteria are able to escape skin immunity and even reside inside