Living in Your Skin: Microbes, Molecules, and Mechanisms

Abstract

Human skin functions as a physical, chemical, and immune barrier against the external environment while also providing a protective niche for its resident microbiota, known as the skin microbiome. Cooperation between the microbiota, host skin cells, and the immune system is responsible for maintenance of skin health, and a disruption to this delicate balance, such as by pathogen invasion or a breach in the skin barrier, may lead to impaired skin function. In this minireview, we describe the role of the microbiome in microbe, host, and immune interactions under distinct skin states, including homeostasis, tissue repair, and wound infection. Furthermore, we highlight the growing number of diverse microbial metabolites and products that have been identified to mediate these interactions, particularly those involved in host-microbe communication and defensive symbiosis. We also address the contextual pathogenicity exhibited by many skin commensals and provide insight into future directions in the skin microbiome field.

Keywords: host-microbe interaction; microbial ecology; skin microbiome; specialized metabolite; wound infection.

FIG 1

Skin state and age influence host-microbiota interactions. In early life, colonization of neonate skin by commensals contributes to development of the immune system and commensal-specific tolerance. During steady state, the skin microbiota is sensed by skin cells and immune cells, inducing a noninflammatory T cell response that leads to enhanced barrier function. After a skin barrier breach, a distinct wound-healing cascade is initiated. However, colonization of the wound bed and biofilm formation by commensals and occasionally pathogens can disrupt the highly coordinated wound-healing response and lead to delayed healing. Lastly, as the skin ages in late life, a gradual loss of function in the physical, chemical, and immune properties of the skin leads to a shifted skin microbiome and susceptibility to infection.

FIG 2

Metabolite-mediated interactions in the skin. The skin microbiota, which colonizes the skin and its appendages both epidermally and subepidermally, produces chemically diverse metabolites, which may be synthesized de novo or metabolized from host-derived molecules. These metabolites confer numerous benefits for the host, including pathogen inhibition, immune education and homeostasis, or even anti-tumor activity. However, under certain conditions, microbial products may promote an inflammatory response. Further, metabolites derived from the host can modulate commensal metabolism, demonstrating the bi-directionality of host-microbiota interactions on the skin.

FIG 3

Pathobionts in the healthy skin microbiome. The average abundance of select pathobionts across 12 skin sites is shown. Sites are classified into sebaceous, moist, dry, or foot microenvironments. The data represent 11 to 17 healthy volunteer samples per skin site for bacterial abundance calculations and 2 to 9 healthy volunteer samples per skin site for fungal abundance calculations. Relative abundance data is from Tables S3 and S5 from reference .