Probiotic supplementation reduces IL-6 and improves clinical outcomes in patients with mild-to-moderate COPD: a randomized placebo-controlled trial

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by persistent inflammation and progressive airflow limitation. Emerging evidence highlights the gut-lung axis as a potential therapeutic target, with probiotics proposed to modulate Th17-related inflammatory pathways. METHODS: In this randomized, double-blind, placebo-controlled trial, 50 patients with mild-to-moderate COPD were enrolled; 44 completed the 8-week intervention (23 probiotics, 21 placebo). Participants received either a multistrain probiotic formulation or placebo. Outcomes included spirometry, COPD Assessment Test (CAT), modified Medical Research Council (mMRC) dyspnea scale, and serum IL-6, IL-17, and TGF-β levels. RESULTS: Probiotic supplementation significantly improved FEV1 and FVC within the intervention group, although between-group spirometric differences were not significant. IL-6 levels declined significantly following probiotic therapy, with a significantly greater reduction compared to placebo, whereas IL-17 and TGF-β remained unchanged. CAT scores improved significantly in the probiotic group, exceeding the minimal clinically important difference and demonstrating a significant between-group effect. No significant change was observed in mMRC scores. CONCLUSION: Eight weeks of probiotic supplementation was associated with reduced systemic IL-6 levels and clinically meaningful improvement in patient-reported outcomes in mild-to-moderate COPD. These findings support a potential adjunctive role for probiotics and warrant larger mechanistic trials. TRIAL REGISTRATION: Registered on 26 December 2024 in the Iranian Registry of Clinical Trials (IRCT), registration number IRCT20241211064025N1.