Low diversity and instability of the sinus microbiota over time in adults with cystic fibrosis

Abstract

Background: Chronic rhinosinusitis (CRS) is a common, yet underreported and understudied manifestation of upper respiratory disease in people with cystic fibrosis (CF). There are currently no standard of care guidelines for the management of CF CRS, but treatment of upper airway disease may ameliorate lower airway disease. We sought to inform future treatment guidelines by determining whether changes to sinus microbial community diversity and specific taxa known to cause CF lung disease are associated with increased respiratory disease and inflammation. Methods: We performed 16S rRNA gene sequencing, supplemented with cytokine analyses, microscopy, and bacterial culturing, on samples from the sinuses of 27 adults with CF CRS at the University of Pittsburgh CF Sinus Clinic. At each study visit, participants underwent endoscopic paranasal sinus sampling and clinical evaluation. We identified key drivers of microbial community composition and evaluated relationships between diversity and taxa with disease outcomes and inflammation. Findings: Sinus community diversity was low and the composition was unstable, with many participants exhibiting alternating dominance between Pseudomonas aeruginosa and Staphylococci over time. Despite a tendency for dominance by these two taxa, communities were highly individualized and shifted composition during exacerbation of sinus disease symptoms. Exacerbations were also associated with communities dominated by Staphylococcus spp. Reduced microbial community diversity was linked to worse sinus disease and the inflammatory status of the sinuses (including increased IL-1β). Increased IL-1β was also linked to worse sinus endoscopic appearance, and other cytokines were linked to microbial community dynamics. Interpretation: To our knowledge, this is the largest longitudinal study of microbial communities and cytokine secretion in CF CRS. Our work revealed previously unknown instability of sinus microbial communities and a link between inflammation, lack of microbial community diversity, and worse sinus disease.

Temperature Influences Commensal-Pathogen Dynamics in a Nasal Epithelial Cell Co-culture Model

“…For S. aureus, we evaluated the thoroughly studied methicillinresistant strain USA300 LAC that is representative of difficult-to-treat S. aureus strains encountered in CRS (47). We utilized two clinical isolates of Corynebacterium from CRS patients (16,48), Corynebacterium propinquum and Corynebacterium pseudodiphtheriticum, due to their prevalence and high relative abundance in the URT (7). We also tested the Corynebacterium glutamicum strain ATCC 13032, a well-characterized and commonly used industrial strain, to serve as a comparison for the airway-adapted Corynebacterium clinical isolates' growth in vitro.…”