{"doi":"10.1101/2022.01.18.476814","title":"Low diversity and instability of the sinus microbiota over time in adults with cystic fibrosis","abstract":"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’s 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-1 β ). Increased IL-1 β 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. Funding Cystic Fibrosis Foundation and US National Institutes of Health. Research in Context Evidence before this study A search of the PubMed database on October 11, 2021 with the terms [cystic fibrosis sinus microbiome] yielded 16 results, and we have identified seven primary research articles on the CF CRS microbiome (including re-analyses of existing datasets). Most are cross-sectional cohort analyses, along with one prior longitudinal study of four adults at the University of Auckland, New Zealand. Together, these prior studies reveal similarities between CF CRS and CF sputum microbiomes, including low community diversity associated with sinus disease, the presence of common CF-associated microbes in the sinuses, and prevalence of sinus communities dominated by P. aeruginosa or Staphylococcus aureus . High levels of IL-1 β are linked to the presence of nasal polyps in CF CRS, and polymorphisms in the IL-1 receptor antagonist gene are associated with risk of CRS outside of the context of CF. Two prior studies of this cohort have been performed by our laboratory. One describes clinical indicators of CF sinus disease and the other links sinus infection biogeography to P. aeruginosa evolutionary genomics. Added value of this study Our study is the first to examine longitudinal relationships between the host immune response (through cytokine profiling) and microbiota dynamics in CF CRS, including linking elevated IL-1 β to worse sinus disease through reduced sinus microbial community diversity. The longitudinal nature of our study also allowed us to uncover striking temporal instability of microbial communities in approximately half of our cohort’s sinus microbial communities over two years, including switching between communities dominated by P. aeruginosa and Staphylococcus spp. This instability could hinder attempts to link the relative abundance of taxa to clinical outcomes of in","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":302528,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9522,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":29119,"name":"Kelvin Li","orcid":"0000-0003-3922-5664","position":1,"is_corresponding":false},{"id":511587,"name":"Megan R. Kiedrowski","orcid":"0000-0003-4610-182X","position":2,"is_corresponding":false},{"id":499892,"name":"Anna C. Zemke","orcid":"0000-0002-7722-6708","position":3,"is_corresponding":false},{"id":263845,"name":"Jeffrey A. Melvin","orcid":"0000-0003-2864-365X","position":4,"is_corresponding":false},{"id":575963,"name":"John Allphin Moore","orcid":"0000-0001-7599-0203","position":5,"is_corresponding":false},{"id":534853,"name":"S. Atteih","orcid":"0009-0006-0481-0539","position":6,"is_corresponding":false},{"id":360800,"name":"Adam Fitch","orcid":"0000-0002-6332-709X","position":7,"is_corresponding":false},{"id":906631,"name":"Matthew DuPont","orcid":null,"position":8,"is_corresponding":false},{"id":681579,"name":"Christopher D. Manko","orcid":"0000-0002-3078-3734","position":9,"is_corresponding":false},{"id":682587,"name":"Madison L. Weaver","orcid":null,"position":10,"is_corresponding":false},{"id":906632,"name":"Jordon R. Gaston","orcid":null,"position":11,"is_corresponding":false},{"id":295193,"name":"John F. Alcorn","orcid":"0000-0001-5997-7711","position":12,"is_corresponding":false},{"id":313765,"name":"Alison Morris","orcid":"0000-0002-7290-6536","position":13,"is_corresponding":false},{"id":19811,"name":"Barbara A. Methé","orcid":"0000-0001-8711-1448","position":14,"is_corresponding":false},{"id":575964,"name":"Stella E. Lee","orcid":"0000-0001-6563-6606","position":15,"is_corresponding":false},{"id":263846,"name":"Jennifer M. Bomberger","orcid":"0000-0003-4767-6238","position":16,"is_corresponding":false},{"id":310266,"name":"Catherine R. Armbruster","orcid":"0000-0003-0795-802X","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-19T00:32:16.279991Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}