Abstract / Summary
Abstract Background Chronic obstructive pulmonary disease (COPD) has important extrapulmonary manifestations, but whether pretreatment intestinal bacterial profiles carry clinically relevant information in hospitalized patients remains unclear. Methods This cross-sectional study included 30 hospitalized patients with COPD and 30 patients hospitalized with other respiratory diseases. Fresh stool was collected within 24 h of admission and before antibiotics or systemic glucocorticoids were administered. Bacterial 16S rRNA gene V3–V4 sequencing was used to characterize community organization, identify exact-sequence associations and develop a classifier under repeated nested cross-validation. A complementary genome-level classifier was developed and evaluated in separately recruited cohorts from a public metagenomic study. Results Patients with COPD showed higher Simpson and inverse Simpson diversity (BH q = 0.0175 and 0.005, respectively) and altered Bray–Curtis community composition (PERMANOVA R² = 0.0550, p = 0.001). Among 56 directionally concordant exact-sequence candidates, 49 were supported by both technical-adjustment and centered-log-ratio analyses, and the 12 highest-ranked sequences retained their associations after non-chimeric reconstruction. The local exact-sequence classifier achieved a repeated nested cross-validated ROC-AUC of 0.8891 (95% CI, 0.8137–0.9510). In the public evaluation cohort, the complementary genome-level classifier achieved a ROC-AUC of 0.9205 (95% CI, 0.8182–0.9943), with 93.75% sensitivity and 72.73% specificity. Conclusions Pretreatment stool bacterial profiles captured a distinct COPD-associated intestinal phenotype and discriminated COPD from other respiratory diseases in hospitalized patients. The prioritized 12-sequence signature and complementary public metagenomic model provide convergent evidence for the clinical potential of stool microbial features as adjunctive markers of COPD.