INTRODUCTION

Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease affecting up to 20% of children and 10% of adults worldwide [1]. Conventional treatments, such as corticosteroids and calcineurin inhibitors, provide symptomatic relief but are often limited by safety concerns and relapse rates [2].

The role of the skin microbiome in AD pathogenesis has garnered increasing attention, particularly the dominance of Staphylococcus aureus and the associated immune dysregulation [3]. Microbiome-based interventions, including probiotics, prebiotics, synbiotics, and, most recently, postbiotics, represent a paradigm shift in dermatologic therapy. Postbiotics, defined as non-viable microbial cells, cell components, or metabolites that confer health benefits, provide stability, safety, and targeted activity compared to live biotics [4].

CONCEPTUAL FRAMEWORK: THE POSTBIOTIC EFFICACY HIERARCHY (PEH)

We propose the Postbiotic Efficacy Hierarchy (PEH), a novel conceptual model to stratify postbiotics by mechanistic evidence, clinical efficacy, and translational readiness (Fig. 1). The key postbiotics and their positions in the PEH are summarized in Table 1. This three-tiered framework categorizes postbiotics as:

Figure 1: Conceptual framework of the Postbiotic Efficacy Hierarchy (PEH).

Table 1: Postbiotic efficacy hierarchy (PEH).

By contextualizing emerging data within this hierarchy, clinicians and researchers can better assess therapeutic potential and prioritize agents for clinical translation.

MECHANISTIC INSIGHTS OF KEY AGENTS

Postbiotics act through diverse mechanisms:

These pathways are summarized in Table 2 and illustrated schematically in Figure 2.

Table 2: Comparative characteristics of probiotics and postbiotics.

Figure 2: Mechanistic pathways of selected postbiotics in AD.

Mechanistic differences across key postbiotics used in AD are detailed in Table 3.

Table 3: Mechanistic profile of key postbiotics used in AD.

Clinical Evidence

Several clinical studies have highlighted the translational relevance of postbiotics:

Emerging data further suggest that biofilms, which reinforce microbial resilience, may reduce therapeutic efficacy; targeting them with specific postbiotics could enhance outcomes [12].

Clinical Translation Roadmap (2025–2030)

We propose a phased roadmap for postbiotic integration into dermatology (Fig. 3). A detailed phase-wise roadmap and expected milestones for clinical translation are presented in Table 5.

Figure 3: Clinical translation roadmap for postbiotics in dermatology.

	Table 4: Summary of recent clinical trials of postbiotics in AD (2024–2025).
	Table 5: Clinical translation roadmap for postbiotics in AD (2025–2030).

This roadmap aligns with the PEH framework and bridges preclinical promise to bedside application.

Conclusion

Postbiotics represent a promising new era of precision microbiome therapy in AD. Through mechanistic diversity, clinical safety, and formulation stability, they hold potential advantages over probiotics. The PEH framework and translational roadmap provide structured pathways for advancing research and clinical adoption.

Future studies should focus on multicenter, biomarker-integrated trials, and consider biofilm-targeting strategies to optimize therapeutic benefit.

REFERENCES

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