Bacterial-Derived Immunomodulators as a Preventive Strategy for Viral Respiratory Tract Infections and Associated Wheezing or Asthma in Children: A Targeted Narrative Review

BACKGROUND/OBJECTIVES: Respiratory tract infections (RTIs) are a leading cause of morbidity in children under five, with over 75% experiencing recurrent episodes and an increased risk of asthma by school age, particularly following respiratory syncytial virus (RSV) and rhinovirus (RV) infections. While current therapies primarily address acute symptoms, effective preventive strategies remain limited. Bacterial-derived immunomodulators have emerged as promising interventions, but their mechanisms and pediatric clinical evidence remain incompletely characterized. This narrative review examines preclinical mechanisms and clinical findings for four such agents, contextualizing current evidence and identifying key gaps. METHODS: CRL1505 were included. Outcomes of interest comprised immunological mechanisms, RTI incidence, wheezing, and asthma-related outcomes. RESULTS: All four agents share convergent immunomodulatory mechanisms involving epithelial barrier reinforcement, innate immune activation, and adaptive immune modulation. OM-85 has the most extensive preclinical evidence. PMBL enhances epithelial repair via the IL-23/IL-22 axis, MV130 induces trained immunity, and CRL1505 acts through the gut-lung axis. Clinical evidence varies markedly, with OM-85 showing the most comprehensive data (18 RCTs and 7 meta-analyses), followed by PMBL and MV130, while evidence for CRL1505 remains predominantly preclinical. CONCLUSIONS: Despite variable evidence maturity, these agents share a coherent mechanistic rationale and favorable safety profiles, with ongoing studies expected to clarify their clinical role in early-life respiratory prevention.