Probiotic-Based Strategies for Respiratory Vaccination: Immunological Mechanisms and Clinical Trial Progress

The gut microbiome plays a pivotal role in shaping both innate and adaptive immune responses, with growing evidence linking microbial composition to vaccine efficacy, particularly in respiratory infections. Probiotics, defined as live microorganisms that confer health benefits, have emerged as promising tools to modulate immunity through mucosal and systemic pathways. This review explores the mechanisms by which probiotics enhance host immunity, including activation of pattern recognition receptors, modulation of cytokine profiles, and promotion of regulatory T cells and IgA production. The gut-lung axis is highlighted as a key pathway in mucosal defense against respiratory pathogens. Beyond immunomodulation, probiotics are being explored as vaccine adjuvants and vectors. Clinical and preclinical studies suggest certain strains can improve vaccine responses and reduce respiratory infection severity. A growing number of trials are evaluating these approaches, although findings remain variable. Key challenges include strain specificity, dosing optimization, and inconsistent efficacy across populations. Continued research is needed to clarify their role and advance probiotic-based strategies as accessible tools for respiratory disease prevention.