Exploratory randomized trial of the bacterial lysate Qipian in stable COPD: peripheral inflammatory, gut and airway microbiota, and fecal metabolomic changes

Introduction To explore Qipian-associated changes in clinical symptoms, systemic inflammation, microbiota, and metabolomic profiles in patients with stable chronic obstructive pulmonary disease (COPD). Method This exploratory study enrolled 40 patients with stable COPD who completed 12 weeks of follow-up (Qipian group: n = 22; control group: n = 18). Key assessments included: pulmonary function (FEV1/FVC, FEV1, FEV1%, FVC, FEF 25−−75 %), clinical symptoms (mMRC dyspnea scale, CAT questionnaire), inflammatory markers, gut and airway microbiota analysis (16S rRNA sequencing for α/β-diversity and taxonomic profiling), untargeted metabolomics (LC-MS-based differential metabolite screening and KEGG pathway enrichment). Result After treatment, the mMRC and CAT scores in the Qipian group showed a decreasing trend compared to the control group ( P = 0.156 and P = 0.055). No statistically significant differences were observed in pulmonary function parameters (all P > 0.05). Inflammatory analysis revealed a significant reduction in NLRP3 expression in the Qipian group compared to controls ( P < 0.001). IL-13 expression decreased significantly compared with pre-treatment levels ( P = 0.034), accompanied by a reduction in serum IL-13 protein levels. Microbiome profiling demonstrated that, compared to the control group, the β-diversity of the gut microbiota in the Qipian group significantly separated after treatment, with an increased relative abundance of potentially beneficial taxa, including Limosilactobacillus and Lactobacillus , and a decreased abundance of potentially pathogenic-associated taxa, including Escherichia-Shigella and Streptococcus . Similarly, the β diversity of the airway microbiota was significantly distinct, showing increased relative abundance of potentially beneficial or commensal-associated taxa such as Veillonella and Prevotella , and decreased abundance of potentially pathogenic-associated taxa such as Streptococcus . Metabolomic profiling identified significant upregulation of L-glutamic acid and L-glutamine. Exploratory correlation analyses suggested associations among selected metabolites, microbiota taxa, and inflammatory markers. Conclusion In this exploratory randomized controlled trial, Qipian was associated with non-significant trends toward symptom improvement and with changes in selected inflammatory markers, gut and airway microbiota, and gut metabolites in patients with stable COPD. These findings suggest Qipian-associated biological changes along the gut–lung axis, involving microbial community remodeling, microbiota-related metabolic alterations, and changes in NLRP3/caspase-1- and IL-13-related inflammatory signaling. However, the clinical outcomes did not reach statistical significance, and these findings should be interpreted as hypothesis-generating rather than confirmatory evidence of clinical efficacy. Trial Registration Chinese Clinical Trial Registry, ChiCTR2100054037. registered on 07 December, 2021.