Crosstalk between skin microbiota and immune system in health and disease Original paper

What was reviewed?

This paper is a narrative review that examined the bidirectional crosstalk between the skin microbiota and the host immune system in health and disease. The authors synthesized experimental, translational, and clinical evidence presented during a National Institute of Allergy and Infectious Diseases–hosted workshop to define how skin-resident microorganisms actively regulate immune development, barrier integrity, and inflammatory responses. Rather than framing the skin microbiome as a static collection of commensals, the review emphasized it as a dynamic ecological system whose composition and function are shaped by immune signaling, host genetics, and environmental exposures. The review also highlighted critical gaps in knowledge that currently limit clinical translation, particularly regarding strain-level specificity and long-term microbiome-based interventions.

Who was reviewed?

The review integrated findings from human observational studies, patient cohorts with inflammatory and infectious skin diseases, and a broad range of animal and in vitro models. Human data included individuals with atopic dermatitis, primary immunodeficiencies such as DOCK8 deficiency and hyper-IgE syndrome, chronic wounds, parasitic skin infections, and hospital-acquired fungal colonization. These observations were complemented by mechanistic studies using germ-free and gnotobiotic mice, human skin xenografts, organoid systems, and metagenomic analyses of healthy and diseased skin. Together, these sources allowed the authors to connect immune dysfunction, microbial dysbiosis, and clinical outcomes.

What were the most important findings?

The review demonstrated that skin commensals actively instruct immune tolerance and protective immunity, particularly during early life. Major microbial associations included Staphylococcus epidermidis, coagulase-negative staphylococci, Corynebacterium, Cutibacterium, and the skin mycobiota dominated by Malassezia. These organisms modulated immunity through microbial metabolites, lipoteichoic acid, and pattern recognition receptor signaling in keratinocytes and immune cells. The authors showed that commensal-driven induction of regulatory T cells, innate-like T cells such as MAIT and NKT cells, and antimicrobial peptides including cathelicidins and β-defensins were essential for maintaining barrier homeostasis. Dysbiosis shifted this balance toward inflammation, with overgrowth of Staphylococcus aureus strongly associated with atopic dermatitis severity, impaired filaggrin expression, and heightened Th2-driven inflammation.

The review also highlighted how fungal dysbiosis and altered lipid metabolism contributed to inflammatory cytokine production and delayed wound healing. Importantly, the authors presented evidence that some commensal strains produce antimicrobial molecules and quorum-sensing inhibitors that suppress pathogens and reduce disease severity, underscoring strain-level functional specificity.

What are the greatest implications of this review?

For clinicians, this review establishes the skin microbiome as an active immune organ whose disruption directly contributes to inflammatory skin disease, infection susceptibility, and impaired healing. Therapeutic strategies that preserve or restore beneficial skin commensals offer a path toward targeted, microbiome-based dermatologic care rather than broad antimicrobial suppression.