Impact of Nocardia Infection on Airway Microbiota in Lung Transplant Recipients: A Single-center, Retrospective Observational Study

Objective: To investigate the impact of Nocardia infection on the airway microbiota composition in lung transplant recipients (LTRs) using mNGS and evaluate associations between microbial alterations and clinical parameters.. Methods : This single-center, retrospective cohort study analyzed 679 LTRs (2015–2024), including 20 Nocardia-infected patients (experimental group, EG), 40 matched controls, and 16 post-treatment group (TG) cases. Bronchoalveolar lavage fluid (BALF) was subjected to mNGS to characterize microbial composition. Multi-modal were applied to analyze integrated α/β-diversity metrics, LEfSe biomarker identification, SparCC co-occurrence networks, and clinical parameter correlations (NCT06594133). Results: Microbiome analysis demonstrated comparable alpha diversity but distinct beta diversity profiles (P=0.025) between groups. The EG exhibited significant enrichment of Nocardia species (predominantly N. farcinica and N. cyriacigeorgica ), alongside decreased Rothia mucilaginosa and Burkholderia species versus controls. Therapeutic intervention substantially reduced Nocardia abundance in treated subjects. Network analysis revealed class_Caudoviricetes displayed inverse associations with Nocardia , Achromobacter , Mastadenovirus , and Yersinia . Nocardia-centered subnet showed positive correlations with Enterococcus , Mastadenovirus , and Yersinia , contrasting with negative correlations involving Capnocytophaga , Rothia , and class_Caudoviricetes. In EG, a robust positive correlation was found of CD4⁺ T-cell counts and the CD4/CD8 ratio with serum IgA, IgM, and IgG (each p <0.05). Spearman analysis linked N. farcinica and N. cyriacigeorgica inversely to CD4⁺ count and albumin; N. farcinica also inversely correlated with IgG, IgA, total lymphocyte count, and hemoglobin; and N. cyriacigeorgica inversely correlated with the CD4/CD8 ratio and positively with CD8⁺ T cells. Conclusions: Nocardia infection induces significant alterations in the airway microbiota of LTRs, characterized by Nocardia enrichment and specific commensal depletion. These microbial shifts are strongly associated with host immune and nutritional status. Our findings highlight the critical role of airway microbial dysbiosis in Nocardia infection pathogenesis and suggest microbiota-targeted strategies that down-regulation the immunosuppressants might be a potential adjunct strategy in Nocardia infection in lung transplant recipients.