Low Diversity and Instability of the Sinus Microbiota over Time in Adults with Cystic Fibrosis
ABSTRACT Chronic rhinosinusitis (CRS) is a common, yet underreported and understudied manifestation of upper respiratory disease in people with cystic fibrosis (CF). Recently developed standard of care guidelines for the management of CF CRS suggest treatment of upper airway disease may ameliorate l...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2022-10-01
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| Series: | Microbiology Spectrum |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/spectrum.01251-22 |
| _version_ | 1811329705888972800 |
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| author | Catherine R. Armbruster Kelvin Li Megan R. Kiedrowski Anna C. Zemke Jeffrey A. Melvin John Moore Samar Atteih Adam C. Fitch Matthew DuPont Christopher D. Manko Madison L. Weaver Jordon R. Gaston John F. Alcorn Alison Morris Barbara A. Methé Stella E. Lee Jennifer M. Bomberger |
| author_facet | Catherine R. Armbruster Kelvin Li Megan R. Kiedrowski Anna C. Zemke Jeffrey A. Melvin John Moore Samar Atteih Adam C. Fitch Matthew DuPont Christopher D. Manko Madison L. Weaver Jordon R. Gaston John F. Alcorn Alison Morris Barbara A. Methé Stella E. Lee Jennifer M. Bomberger |
| author_sort | Catherine R. Armbruster |
| collection | DOAJ |
| description | ABSTRACT Chronic rhinosinusitis (CRS) is a common, yet underreported and understudied manifestation of upper respiratory disease in people with cystic fibrosis (CF). Recently developed standard of care guidelines for the management of CF CRS suggest treatment of upper airway disease may ameliorate lower airway disease. We sought to determine whether changes to sinus microbial community diversity and specific taxa known to cause CF lung disease are associated with increased respiratory disease and inflammation. 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 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. 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 interleukin-1β [IL-1β]). Increased IL-1β was also linked to worse sinus endoscopic appearance, and other cytokines were linked to microbial community dynamics. Our work revealed previously unknown instability of sinus microbial communities and a link between inflammation, lack of microbial community diversity, and worse sinus disease. IMPORTANCE Together with prior sinus microbiota studies of adults with CF chronic rhinosinusitis, our study underscores similarities between sinus and lower respiratory tract microbial community structures in CF. We show how community structure tracks with inflammation and several disease measures. This work strongly suggests that clinical management of CRS could be leveraged to improve overall respiratory health in CF. Our work implicates elevated IL-1β in reduced microbiota diversity and worse sinus disease in CF CRS, suggesting applications for existing therapies targeting IL-1β. Finally, the widespread use of highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy has led to less frequent availability of spontaneous expectorated sputum for microbiological surveillance of lung infections. A better understanding of CF sinus microbiology could provide a much-needed alternative site for monitoring respiratory infection status by important CF pathogens. |
| first_indexed | 2024-04-13T15:48:40Z |
| format | Article |
| id | doaj.art-7a2bc36f5e39472e9ab36c7cf0ad33b9 |
| institution | Directory Open Access Journal |
| issn | 2165-0497 |
| language | English |
| last_indexed | 2024-04-13T15:48:40Z |
| publishDate | 2022-10-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | Microbiology Spectrum |
| spelling | doaj.art-7a2bc36f5e39472e9ab36c7cf0ad33b92022-12-22T02:40:54ZengAmerican Society for MicrobiologyMicrobiology Spectrum2165-04972022-10-0110510.1128/spectrum.01251-22Low Diversity and Instability of the Sinus Microbiota over Time in Adults with Cystic FibrosisCatherine R. Armbruster0Kelvin Li1Megan R. Kiedrowski2Anna C. Zemke3Jeffrey A. Melvin4John Moore5Samar Atteih6Adam C. Fitch7Matthew DuPont8Christopher D. Manko9Madison L. Weaver10Jordon R. Gaston11John F. Alcorn12Alison Morris13Barbara A. Methé14Stella E. Lee15Jennifer M. Bomberger16Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USACenter for Medicine and the Microbiome, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USADepartment of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USADepartment of Medicine, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USADepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USADepartment of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USADepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USACenter for Medicine and the Microbiome, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USADepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USADepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USADepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USADepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USADepartment of Pediatrics, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USACenter for Medicine and the Microbiome, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USACenter for Medicine and the Microbiome, University of Pittsburgh and University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USADepartment of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USADepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USAABSTRACT Chronic rhinosinusitis (CRS) is a common, yet underreported and understudied manifestation of upper respiratory disease in people with cystic fibrosis (CF). Recently developed standard of care guidelines for the management of CF CRS suggest treatment of upper airway disease may ameliorate lower airway disease. We sought to determine whether changes to sinus microbial community diversity and specific taxa known to cause CF lung disease are associated with increased respiratory disease and inflammation. 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 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. 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 interleukin-1β [IL-1β]). Increased IL-1β was also linked to worse sinus endoscopic appearance, and other cytokines were linked to microbial community dynamics. Our work revealed previously unknown instability of sinus microbial communities and a link between inflammation, lack of microbial community diversity, and worse sinus disease. IMPORTANCE Together with prior sinus microbiota studies of adults with CF chronic rhinosinusitis, our study underscores similarities between sinus and lower respiratory tract microbial community structures in CF. We show how community structure tracks with inflammation and several disease measures. This work strongly suggests that clinical management of CRS could be leveraged to improve overall respiratory health in CF. Our work implicates elevated IL-1β in reduced microbiota diversity and worse sinus disease in CF CRS, suggesting applications for existing therapies targeting IL-1β. Finally, the widespread use of highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy has led to less frequent availability of spontaneous expectorated sputum for microbiological surveillance of lung infections. A better understanding of CF sinus microbiology could provide a much-needed alternative site for monitoring respiratory infection status by important CF pathogens.https://journals.asm.org/doi/10.1128/spectrum.01251-22Pseudomonas aeruginosaStaphylococcuschronic rhinosinusitiscystic fibrosisinflammationmicrobiota |
| spellingShingle | Catherine R. Armbruster Kelvin Li Megan R. Kiedrowski Anna C. Zemke Jeffrey A. Melvin John Moore Samar Atteih Adam C. Fitch Matthew DuPont Christopher D. Manko Madison L. Weaver Jordon R. Gaston John F. Alcorn Alison Morris Barbara A. Methé Stella E. Lee Jennifer M. Bomberger Low Diversity and Instability of the Sinus Microbiota over Time in Adults with Cystic Fibrosis Microbiology Spectrum Pseudomonas aeruginosa Staphylococcus chronic rhinosinusitis cystic fibrosis inflammation microbiota |
| title | Low Diversity and Instability of the Sinus Microbiota over Time in Adults with Cystic Fibrosis |
| title_full | Low Diversity and Instability of the Sinus Microbiota over Time in Adults with Cystic Fibrosis |
| title_fullStr | Low Diversity and Instability of the Sinus Microbiota over Time in Adults with Cystic Fibrosis |
| title_full_unstemmed | Low Diversity and Instability of the Sinus Microbiota over Time in Adults with Cystic Fibrosis |
| title_short | Low Diversity and Instability of the Sinus Microbiota over Time in Adults with Cystic Fibrosis |
| title_sort | low diversity and instability of the sinus microbiota over time in adults with cystic fibrosis |
| topic | Pseudomonas aeruginosa Staphylococcus chronic rhinosinusitis cystic fibrosis inflammation microbiota |
| url | https://journals.asm.org/doi/10.1128/spectrum.01251-22 |
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