Lactic acid bacteria-derived extracellular vesicles as postbiotic modulators of epithelial adhesion and barrier...

Microbiota-targeted strategies are increasingly moving beyond the administration of live microorganisms toward cell-free microbial components with postbiotic potential. Among these, extracellular vesicles released by lactic acid bacteria (LAB-derived EVs) are emerging as biologically active particles capable of transferring bacterial signals to host epithelial and immune cells. However, their effects should not be interpreted as uniform or intrinsically beneficial, because vesicle composition and activity are strongly influenced by bacterial strain, culture conditions, growth phase, isolation procedures and target cell context. In this Perspective, we discuss LAB-derived EVs as candidate postbiotic modulators of epithelial adhesion and barrier homeostasis. We focus on the epithelial interface as an integrated functional unit in which tight junctions, adherens junctions, junctional adhesion molecules, integrin-related cell-matrix adhesion, extracellular matrix remodeling and epithelial-immune communication converge. Evidence, largely derived from Lactobacillus/Lactobacillaceae models, supports the ability of LAB-derived EVs to influence barrier integrity, inflammatory tone, pathogen adhesion and tissue repair. We also propose an exploratory framework based on early transcriptional responses observed in A549 respiratory epithelial cells exposed to an EV-enriched preparation obtained from Lactobacillus fermentum 18A-TV, highlighting a transcriptional signature compatible with transient epithelial remodeling involving junctional, extracellular matrix, integrin-related and repair-associated genes. Future studies should combine standardized EV characterization with protein-level and functional assays to define reproducible potency markers and clarify the therapeutic potential of LAB-derived EVs.