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|Title:||Characterizing age-related changes and protective features in the upper respiratory tract microbiota associated with healthy aging and chronic inflammation|
|Keywords:||aging;older adults;microbiome;nasal;16S rRNA sequencing;local inflammation|
|Abstract:||Background: The upper respiratory tract (URT) is composed of an array of microbes that can contribute to or protect against upper respiratory infections. Older adults (>65 years) are at greatest risk of acquiring respiratory tract infections, particularly pneumococcal infections, resulting in over 7,000 deaths per year in older Canadians. The increased risk of infection may be linked to diversity, high variability, and a decrease in commensal bacteria residing in the URT microbiota. The impact local inflammation has on microbial communities in the nasal cavity is not well defined. Previous research in our laboratory identified 5 dominant microbial profiles in the anterior nares URT microbiota of healthy adults. We also started building a strain collection of commensal bacteria isolated from the URT that may provide protection against pathogenic bacteria, such as S. pneumoniae. Our aim is to characterize microbial changes in the URT microbiota with age-associated changes such as specific health conditions and inflammation to determine which microbes are protective against respiratory infections. Methods: To approach this, we collected nasal samples from 178 community-dwelling adults (18-102 years) throughout 2020 – 2022. Participants provided an additional nasal sample if they were symptomatic during cold/flu season. We collected 99 nasal samples, and 18 nasal fluid samples from 46 adults, over 3 visitations, diagnosed with either osteoarthritis or rheumatoid arthritis, to measure how local inflammatory markers (GM-CSF, Fractalkine, IL-6, IL-1 and TNF) change the nasal microbiota. The samples were processed with 16S rRNA gene sequencing, and bacterial load was measured using qPCR to determine the total 16S rRNA abundance. Phenotypic and liquid assays determine commensal microbes that exhibit resistance to S. pneumoniae colonization. Results: We identified 7 dominant microbial profiles in the aging nasal cavity, which differed statistically with bacterial load and seasonality. We observed higher movement between these profiles within individuals who experienced a respiratory infection. We identified 8 profiles in an inflamed nasal cavity. The composition of these profiles was associated with changes in DMARDS treatment for adults living with rheumatoid arthritis. The difference between microbial profiles in the nasal cavity is due to higher variation and a diverse microbiota. Conclusion: In addition to observing compositional changes with bacterial load, seasonality, and inflammation, we identified protective microbial strains residing in the nasal cavity. This allows us to begin identifying secondary metabolites with inhibitory activity against S. pneumoniae in the URT microbiota and non – harmful properties to the host, to develop novel drug therapeutics to reduce the risk of pneumococcal infections in older Canadians.|
|Appears in Collections:||Open Access Dissertations and Theses|
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|Boron_Dominika_finalsubmission_2022Oct_MSc.pdf||11.26 MB||Adobe PDF||View/Open|
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