Airway Candida diversity in COPD patients and its differential stimulatory effects on lung inflammation in mice

The airway microbiome is altered in chronic obstructive pulmonary disease (COPD) individuals with high fungal diversity, which manifests mainly as an increase in the diversity of Candida genera. Acute exacerbation of COPD (AECOPD) is a crucial process in disease progression. The airway Candida species diversity in AECOPD patients and their differential stimulatory effects on airway inflammation in mice remain unclear. To investigate the diversity of airway Candida species involved in AECOPD and assess their differential effects on airway inflammation in mice. We conducted airway bacterial and fungal microbiota surveys using 16S rRNA (V4 region) sequencing, ITS1 sequencing, and fungal cultures from sputum samples of 63 AECOPD patients. Subsequently, five Candida species isolated from airways were nasally colonized into mice. He staining, qPCR and 16S rRNA V4 region sequencing of mouse lung tissues were performed to explore the host inflammatory responses to different Candida species. Candida species were detected in the sputum of 50 (80.95%) of the 63 volunteers with AECOPD. Candida albicans, Candida glabrata, Candida parapsilosis, Candida orthopsilosis, and Candida dubliniensis were the five most prevalent species. Nasal Candida colonization in mice caused varying degrees of inflammation, with H&E staining scores of 2–7. Mouse body weight decreases significantly on days 11 and 13 after exposure to Candida albicans, Candida krusei, Candida parapsilosis, or Candida tropicalis. After a Candida albicans infection, significant increases in IL-8 and IL-1β in the mouse airways were observed. The mouse lung microbiota shifted after the addition of Candida species, with Prevotella, Streptococcus, Sutterella, Ralstonia, Sphingomonas, and Bradyrhizobiaceae being the genera identified among the six groups. The airways of AECOPD patients exhibit a high diversity of Candida species, each triggering distinct inflammatory patterns in mouse lungs. These findings warrant investigation into species-specific mechanisms in Candida-related COPD.