Skin microbiome and dysbiosis in atopic dermatitis

The skin microbiome is a complex ecosystem composed of bacteria, viruses, fungi, and other microorganisms that play a crucial role in maintaining epidermal barrier integrity and immune homeostasis.1,5 Disruption of microbial balance leads to impaired barrier function, reduced local immune defense, and excessive colonization by pathogenic microorganisms.1,4

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Dysbiosis is considered a major determinant of disease severity in atopic dermatitis.1,3 Numerous studies have demonstrated that S. aureus is isolated from lesional skin in a high proportion of patients with active AD.1,3 Microbial composition differs significantly between flare and remission phases: disease exacerbation is preceded by increased S. aureus colonization and a marked reduction in microbial diversity,3 whereas higher abundance of coagulase-negative staphylococci and protective commensal-derived antimicrobials is associated with milder disease phenotypes.6

 

Genotypic characteristics of Staphylococcus aureus in atopic dermatitis

The strains of S. aureus colonizing the skin of patients with atopic dermatitis may differ genetically and functionally from those detected in non-AD populations, and these differences can correlate with disease severity and host barrier genetics (including filaggrin-related associations).4 Such variability may contribute to differences in virulence factor expression and immune activation in AD.1,7

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These genotypic and functional differences support the pathogenic specificity of S. aureus in atopic dermatitis.1,4,7

 

Mechanisms of barrier disruption and inflammation

In atopic dermatitis, S. aureus exacerbates epidermal barrier damage through multiple virulence factors and host–microbe interactions, thereby amplifying cutaneous inflammation and barrier dysfunction.1 Microbial products and toxins further influence inflammatory pathways linked to AD.1,8

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The secreted cytotoxin α-hemolysin (alpha-toxin) is produced by skin-colonizing S. aureus and has been implicated in immune activation relevant to AD.8 Together, these mechanisms support a role for S. aureus in perpetuating inflammation and barrier impairment in susceptible hosts.1,8

 

Superantigens, pruritus, and steroid resistance

Staphylococcus aureus strains isolated from patients with atopic dermatitis frequently produce superantigens, and infected AD lesions may contain pharmacologically relevant amounts of staphylococcal superantigens.9 Superantigen-driven pathways can promote allergic skin inflammation in experimental models.10

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These superantigens induce massive activation of antigen-presenting cells and T lymphocytes by directly binding to MHC class II molecules and T-cell receptors, bypassing conventional antigen presentation, leading to excessive cytokine production and increased disease activity.10 The presence of superantigens in infected AD lesions further supports their contribution to disease exacerbation.9

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Superantigen-related immune activation has also been proposed as a mechanism that can reduce responsiveness to immunosuppressive therapy in inflammatory skin disease.9,10

 

Neural mechanisms of pruritus

Experimental studies have demonstrated that S. aureus can directly induce pruritus through interaction with peripheral nerve signaling. In particular, inhibition of protease-activated receptor-1 (PAR1) signaling reduces itch induced by S. aureus, supporting a neuroimmune itch pathway relevant to AD symptomatology.11

 

Antimicrobial defense, biofilm formation, and persistence

Rapid elimination of S. aureus from the skin depends in part on endogenous antimicrobial peptides; in atopic dermatitis, deficiencies in antimicrobial peptide responses are associated with increased susceptibility to skin infections and colonization.12 In addition, a deficiency in protective antimicrobials produced by commensal skin bacteria has been demonstrated in AD, further supporting a dysbiosis-driven vulnerability to S. aureus overgrowth.13

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Staphylococcus aureus persistence is also facilitated by biofilm formation. Staphylococcal biofilms have been demonstrated in atopic dermatitis and are associated with bacterial persistence and reduced susceptibility to antimicrobial interventions.14

 

Bacteriophages as a novel therapeutic strategy

Conventional systemic and topical antibiotics are frequently used in patients with atopic dermatitis during exacerbations and secondary infections; however, prolonged antibiotic use increases selective pressure on resistant strains and can disrupt the commensal skin microbiota.15,16

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Recent work characterizing the human skin phageome has demonstrated differences between normal and inflamed skin, supporting the concept that alterations in the bacterial–phage ecosystem may be relevant to inflammatory skin conditions, including AD.17 Bacteriophages—viruses that specifically infect bacteria—have therefore emerged as a promising alternative antimicrobial strategy.15-18 Phages exhibit high specificity for target bacteria, bactericidal activity, and the capacity to act at the site of infection; phage-derived enzymes and related mechanisms may also contribute to activity against bacterial biofilms.15,19

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Phage cocktails and personalized (“sur-mesure”) approaches have been proposed to improve efficacy and address host-range limitations.19,20 Key reviews summarize pharmacologic principles, accumulated evidence, and clinical implementation considerations for phage therapy. These properties position phage therapy as a strategic, microbiome-oriented approach for the management of atopic dermatitis.