Dynamic Role of Host Stress Responses in Modulating the Cutaneous Microbiome: Implications for Wound Healing and...

Significance: Humans are under constant bombardment by various stressors, including psychological anxiety and physiologic injury. Understanding how these stress responses influence the innate immune system and the skin microbiome remains elusive due to the complexity of the neuroimmune and stress response pathways. Both animal and human studies have provided critical information upon which to further elucidate the mechanisms by which mammalian stressors impair normal wound healing and/or promote chronic wound progression. Recent Advances: Development of high-throughput genomic and bioinformatic approaches has led to the discovery of both an epidermal and dermal microbiome with distinct characteristics. This technology is now being used to identify statistical correlations between specific microbiota profiles and clinical outcomes related to cutaneous wound healing and the response to pathogenic infection. Studies have also identified more prominent roles for typical skin commensal organisms in maintaining homeostasis and modulating inflammatory responses. Critical Issues: It is well-established that stress-induced factors, including catecholamines, acetylcholine, and glucocorticoids, increase the risk of impaired wound healing and susceptibility to infection. Despite the characterization of the cutaneous microbiome, little is known regarding the impact of these stress-induced molecules on the development and evolution of the cutaneous microbiome during wound healing. Future Directions: Further characterization of the mechanisms by which stress-induced molecules influence microbial proliferation and metabolism in wounds is necessary to identify altered microbial phenotypes that differentially influence host innate immune responses required for optimal healing. These mechanisms may yield beneficial as targets for manipulation of the microbiome to further benefit the host after cutaneous injury.