Some bronchiectasis patients exhibit increased airway abundance of Neisseria spp.
•
The culturable species N. subflava weakens barrier integrity and induces inflammation
•
N. subflava elicits distinct transcriptomic/metabolipidomic signatures in the mouse lung
•
Neisseria-associated pathogenic signatures are observed in bronchiectasis patients
Summary
Neisseria species are frequently identified in the bronchiectasis microbiome, but they are regarded as respiratory commensals. Using a combination of human cohorts, next-generation sequencing, systems biology, and animal models, we show that bronchiectasis bacteriomes defined by the presence of Neisseria spp. associate with poor clinical outcomes, including exacerbations. Neisseria subflava cultivated from bronchiectasis patients promotes the loss of epithelial integrity and inflammation in primary epithelial cells. In vivo animal models of Neisseria subflava infection and metabolipidome analysis highlight immunoinflammatory functional gene clusters and provide evidence for pulmonary inflammation. The murine metabolipidomic data were validated with human Neisseria-dominant bronchiectasis samples and compared with disease in which Pseudomonas-, an established bronchiectasis pathogen, is dominant. Metagenomic surveillance of Neisseria across various respiratory disorders reveals broader importance, and the assessment of the home environment in bronchiectasis implies potential environmental sources of exposure. Thus, we identify Neisseria species as pathobionts in bronchiectasis, allowing for improved risk stratification in this high-risk group.
Graphical abstract
Keywords
Neisseria
microbiome
bronchiectasis
transcriptomics
metabololipidomics
metagenomics
CAMEB
Data and code availability
•
All raw sequencing and metabolipidomic data have been deposited in NCBI-SRA and MetaboLights database (EMBL-EBI) respectively. Public accession numbers associated with 16S rRNA gene amplicon sequencing data, mouse transcriptomic RNA sequencing data, metabolomics and lipidomics data, sputum and environmental metagenomic whole genome shotgun (WGS) data and Neisseria subflava genome assemblies are described in the key resources table.
Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon reasonable request and needs to abide by approved ethical and legal policies.