Postbiotics and extracellular vesicles: Mechanisms of action and clinical promise in respiratory infections and inflammation

Postbiotics are bioactive metabolites and structural components derived from probiotic microorganisms that exert health benefits without the requirement for live bacteria. These include short-chain fatty acids, peptides, polysaccharides, and bacterial cell wall fragments, all of which demonstrate immunomodulatory, anti-inflammatory, and antimicrobial properties. Compared with probiotics, postbiotics are more stable, safer, and increasingly recognized as potential therapeutic agents. Extracellular vesicles (EVs) released by probiotics have likewise emerged as important mediators of host–microbe interactions. In respiratory diseases such as pneumonia, influenza, coronavirus disease 2019 (COVID-19), asthma, cystic fibrosis, tuberculosis, and allergic rhinitis, postbiotics strengthen epithelial barriers, regulate immune responses, disrupt pathogenic biofilms, and enhance the effectiveness of conventional therapies. Their capacity to influence the gut–lung axis further extends their benefits beyond the respiratory system, contributing to systemic immune balance and microbiota homeostasis. Moreover, postbiotics show potential in mitigating antimicrobial resistance by selectively targeting pathogens while preserving commensal microbes. Taken together, the safety, versatility, and therapeutic promise of postbiotics highlight their potential as adjuncts to standard treatments and as innovative strategies for infection control and respiratory health management. • Postbiotics, including SCFAs and bacterial lysates, modulate the gut-lung axis to enhance epithelial barriers and balance Th1/Th2 responses, reducing inflammation in chronic respiratory diseases like asthma and cystic fibrosis. • Probiotic-derived extracellular vesicles regulate IL-17-producing cells and cytokine profiles, demonstrating protective effects against viral infections such as influenza and SARS-CoV-2 in preclinical models. • In tuberculosis and allergic rhinitis, postbiotics exhibit antimicrobial and anti-inflammatory properties, supported by RCTs showing reduced exacerbations and improved immune homeostasis. • By disrupting biofilms and mitigating antibiotic resistance, postbiotics serve as stable, safe adjuncts to standard therapies, with potential to address gaps in managing pulmonary fibrosis and respiratory infections.