Neisseria species as pathobionts in bronchiectasis lipid-metabome data

Little is known about Neisseria species within the bronchiectasis microbiome. Using a bedside to bench approach combining human cohorts, next generation sequencing and systems biology in human and mouse models, we demonstrate that bacteriomes in bronchiectasis, characterized by Neisseria, relate to poor clinical outcomes including exacerbations. Cultivable Neisseria subflava from bronchiectasis promotes loss of epithelial integrity and induces inflammation in primary human epithelium ex vivo. In vivo mouse models of Neisseria subflava infection demonstrate transcriptomic immuno-inflammatory functional gene clusters and pulmonary inflammation through the metabo-lipidome. Systemic change from mouse metabo-lipidomes were validated in Neisseria-dominant bronchiectasis, and were comparable to Pseudomonas-dominant disease, an established bronchiectasis pathogen. Metagenomic surveillance of Neisseria across other respiratory diseases reveal broader significance and, assessment of the home environment in bronchiectasis suggests potential environmental sources of exposure. In summary, we report Neisseria species as pathobionts in bronchiectasis allowing for improved risk-stratification in this high-risk group. <br>