Neisseria species as pathobionts in bronchiectasis
Liang Li, Micheál Mac Aogáin, Tengfei Xu, Tavleen Kaur Jaggi, Louisa Chan, Jing Qu, Lan Wei, Shumin Liao, Hong Sheng Cheng, Holly R. Keir, Alison Dicker, Kai Sen Tan, Wang De Yun, Mariko Siyue Koh, Thun How Ong, Albert Yick Hou Lim, John Abisheganaden, Teck Boon Low, Tidi Hassan, Xiang Long, Peter Wark, Brian G. Oliver, Daniela I. Drautz‐Moses, Stephan C. Schuster, Nguan Soon Tan, Mingliang Fang, James D. Chalmers, Sanjay H. Chotirmall
Abstract
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.