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The composition and functional protein subsystems of the human nasal microbiome in granulomatosis with polyangiitis: a pilot study.

  • Wagner, Josef
  • Harrison, Ewan M
  • Martinez Del Pero, Marcos
  • Blane, Beth
  • Mayer, Gert
  • Leierer, Johannes
  • Gopaluni, Seerapani
  • Holmes, Mark
  • Parkhill, Julian
  • Peacock, Sharon
  • Jayne, David
  • Kronbichler, Andreas
Publication Date
Oct 22, 2019
Apollo - University of Cambridge Repository
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Background Ear, nose and throat involvement in granulomatosis with polyangiitis (GPA) is frequently the initial disease manifestation. Previous investigations have observed a higher prevalence of Staphylococcus aureus in patients with GPA and chronic nasal carriage has been linked with an increased risk of disease relapse. In this cross-sectional study we investigated changes in the nasal microbiota including a detailed analysis of Staphylococcus spp. by shot gun metagenomics in patients with active and inactive granulomatosis with polyangiitis (GPA). Shot gun metagenomic sequence data were also used to identify protein encoding genes within the SEED database and the abundance of proteins then correlated with the presence of bacterial species on an annotated heatmap. Results The presence of S. aureus in the nose as assessed by culture was more frequently detected in patients with (66.7%) compared to inactive GPA (34.1%). Beta-diversity analysis of nasal microbiota by bacterial 16S rRNA profiling revealed a different composition between GPA patients versus healthy controls (p=0.039). Beta-diversity analysis of shotgun metagenomic sequence data for Staphylococcus spp. revealed a different composition between active GPA patients versus healthy controls and disease controls (p=0.0007 and p=0.0023, respectively) and between healthy controls versus inactive GPA patients and household controls (p=0.0168 and p=0.0168, respectively). Patients with active GPA had a higher abundance of S. aureus, mirroring the culture data, while healthy controls had a higher abundance of S. epidermidis. Staphylococcus pseudintermedius, generally assumed to be a pathogen of cats and dogs, showed an abundance of 13% among the Staphylococcus spp. in our cohort. During long term follow-up of patients with inactive GPA at baseline, a higher S. aureus abundance was not associated with an increased relapse risk. Functional analyses identified ten SEED protein subsystems that differed between the groups. Most significant associations were related to chorismate synthesis and involved in the vitamin B12 pathway. Conclusion Our data revealed a distinct dysbiosis of the nasal microbiota in GPA patients compared to disease and health controls. Metagenomic sequencing demonstrated that this dysbiosis in active GPA patients is manifested by increased abundance of S. aureus and a depletion of S. epidermidis, further demonstrating the antagonist relationships between these species. SEED functional protein subsystem analysis identified an association between the unique bacterial nasal microbiota clusters seen mainly in GPA patients and an elevated abundance of genes associated with chorismate synthesis and vitamin B12 pathways. Further studies are required to further elucidate the relationship between the biosynthesis genes and the associated bacterial species. / NIHR Cambridge Comprehensive Biomedical Research Centre Immunity, Infection and Inflammation theme

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