Gut–Lung Axis Microbiome Dysbiosis and Cross-Domain Network Analysis in Bronchiectasis Complicated by Invasive Pulmonary Aspergillosis

Wei Zhao,1 Chunlai Feng,1 Yilei Zhang,1 Linlin Wang21Department of Respiratory and Critical Care Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, People’s Republic of China; 2Department of Medicine, Dinfectome Inc, Nanjing, People’s Republic of ChinaCorrespondence: Chunlai Feng, Department of Respiratory and Critical Care Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, People’s Republic of China, Tel +86-15961196958, Email [email protected]: To explore the clinical significance of pulmonary and gut microbiota in patients with bronchiectasis (BE) with invasive pulmonary aspergillosis (BE-IPA). By analyzing cross-domain microbial networks, we aimed to elucidate the bidirectional interaction mechanisms of the gut–lung axis, provide a theoretical basis for clinical diagnosis, and to identify potential candidate biomarkers and inform future mechanistic studies from a microbiomic perspective.Patients and Methods: We retrospectively examined 78 patients with BE, divided into BE without IPA (n = 37) and BE-IPA (n = 41) groups. Bronchoalveolar lavage fluid and anal swabs were collected. Metagenomic next-generation sequencing was used to analyze microbiota diversity, species composition, and metabolic pathways between the groups. Clinical data were evaluated for correlations with specific taxa, and a cross-domain microbial co-occurrence network was constructed.Results: Compared to the BE group, the BE-IPA group exhibited significant differences in pulmonary microbiota β-diversity (P < 0.05) and increased gut microbiota evenness (Shannon and Simpson indices, P < 0.05). Aspergillus and species-level Aspergillus fumigatus were significantly enriched in the BE-IPA group lungs, whereas Parabacteroides and Hoylesella were enriched in the gut. The relative abundance of core gut commensals such as Bacteroides dorei was negatively correlated with Acute Physiology and Chronic Health Evaluation II score. The BE-IPA group showed 17 upregulated gut metabolic pathways (P < 0.05), primarily involving lipopolysaccharide biosynthesis and carbohydrate metabolism. Pulmonary A. fumigatus exhibited negative correlations with gut B. dorei and pulmonary Rothia mucilaginosa.Conclusion: The pulmonary microbiota in the BE-IPA group showed a fungal–bacterial symbiotic network centered on A. fumigatus, whereas gut microbiota presented a bacterial co-occurrence network enriched with Parabacteroides. In patients with BE-IPA, pulmonary and gut microbes were associated with multiple clinical indicators and metabolic pathways. These microbiota signatures may aid in the assessment of disease severity in BE-IPA, with the gut commensal B. dorei emerging as a candidate biomarker and a potential subject for future interventional studies.Keywords: bronchiectasis with invasive pulmonary aspergillosis, lung microbiota, gut microbiota, gut–lung axis, metagenomic next-generation sequencing