Postbiotics as Emerging Therapeutics for Allergic Diseases: A Novel Approach Beyond Live Biologics

Allergic diseases, including asthma, atopic dermatitis, allergic rhinitis, and food allergies, are characterized by immune dysregulation, epithelial barrier dysfunction, and exaggerated type 2 inflammation. Although current therapeutic strategies have improved disease management, many treatments remain symptomatic, costly, and insufficiently effective in a substantial proportion of patients. Increasing recognition of the gut-immune axis has shifted attention toward microbiome-derived therapeutic approaches. However, safety concerns and inconsistent clinical outcomes associated with live probiotics have accelerated interest in postbiotics, defined as preparations of inanimate microorganisms and/or their bioactive components that confer health benefits to the host. This comprehensive review summarizes current mechanistic, translational, and clinical evidence regarding the role of postbiotics in allergic diseases. Particular emphasis is placed on immunological checkpoints targeted by postbiotic-derived bioactive molecules, including modulation of Th1/Th2 balance, induction of regulatory T cells, restoration of epithelial barrier integrity, regulation of innate lymphoid cells, and systemic immune signaling through the gut-lung and gut-skin axes. Accumulating evidence indicates that postbiotics-including short-chain fatty acids, cell wall components, extracellular vesicles, exopolysaccharides, and microbial metabolites-can modulate immune responses independently of microbial viability. Preclinical studies consistently demonstrate that postbiotics restore immune tolerance, attenuate allergic inflammation, and improve epithelial barrier function. Clinical studies, particularly in atopic dermatitis, have shown promising but heterogeneous outcomes, highlighting the need for standardized formulations and biomarker-guided patient stratification. Postbiotics represent a mechanistically distinct and potentially safer microbiome-based therapeutic strategy for allergic diseases. Nevertheless, important challenges remain regarding standardization, regulatory harmonization, mechanistic characterization, and long-term clinical validation. Future progress will depend on rigorously designed longitudinal studies, multi-omics integration, and precision medicine approaches to determine whether postbiotics can evolve from adjunctive therapies into disease-modifying interventions.