Gut microbiota–mediated effects of galacto-oligosaccharides on pediatric non-specific chronic cough: clinical and experimental evidence

Non-specific chronic cough (NSCC) is a common pediatric condition with limited effective therapeutic options. Emerging evidence suggests that the gut–lung axis plays a critical role in respiratory diseases. Galacto-oligosaccharides (GOS), as prebiotics, may relieve cough symptoms by modulating gut microbiota and immune responses. Sixty-six children diagnosed with NSCC were enrolled in this study, with 60 completing the trial. Participants were randomly assigned to receive either standard therapy plus maltodextrin (control group) or standard therapy plus GOS 8 g/day (treatment group) for 56 days. Clinical outcomes included cough symptom scores, Visual Analog Scale (VAS) and Fractional exhaled Nitric Oxide (FeNO) levels. Post-treatment stool samples were collected for 16 S rRNA-based gut microbiota profiling. Concurrently, a mouse model of capsaicin-induced chronic cough was established. Mice received daily treatments with GOS (0.5 g/kg), montelukast (10 mg/kg), or PBS for 21 days. Bronchoalveolar lavage fluid (BALF), serum, and lung tissues were collected for histological, immunological, and molecular analyses. GOS supplementation significantly reduced cough symptom scores, accompanied by improvements in FeNO levels. Gut microbiota analysis revealed distinct compositional changes, with increased abundance of beneficial bacteria and reduced pro-inflammatory taxa in the treatment group. In the animal model, GOS markedly alleviated airway inflammation, reduced pro-inflammatory cytokine levels, and preserved lung tissue integrity. These effects were associated with altered gut microbial composition and reduced systemic inflammatory markers. GOS supplementation effectively alleviates non-specific chronic cough in children, potentially by modulating the gut microbiota and reducing pulmonary inflammation via the gut–lung axis. These findings provide translational insights supporting the use of prebiotic interventions in pediatric respiratory diseases.