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Characterisation of the nasal microbiota in granulomatosis with polyangiitis
  1. Rennie L Rhee1,
  2. Antoine G Sreih1,
  3. Catherine E Najem1,
  4. Peter C Grayson2,
  5. Chunyu Zhao3,
  6. Kyle Bittinger3,
  7. Ronald G Collman4,
  8. Peter A Merkel5
  1. 1 Division of Rheumatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  2. 2 Vasculitis Translational Research Program, National Institutes of of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Maryland, USA
  3. 3 Division of Gastroenterology, Hepatology, and Nutrition, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
  4. 4 Division of Pulmonary, Allergy, and Critical Care, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  5. 5 Division of Rheumatology and the Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, USA
  1. Correspondence to Dr Rennie L Rhee, Division of Rheumatology, University of Pennsylvania, Philadelphia, PA 19104, USA; rennie.rhee{at}uphs.upenn.edu

Abstract

Objectives Prior studies have suggested a potential link between nasal microbes and granulomatosis with polyangiitis (GPA; Wegener’s), but these studies relied on culture-dependent methods. This study comprehensively examined the entire community of nasal microbiota (bacteria and fungi) in participants with GPA compared with healthy controls using deep sequencing methods.

Methods 16S rRNA and internal transcribed spacer gene sequencing were performed on nasal microbial DNA isolated from nasal swabs of 60 participants with GPA and 41 healthy controls. Alpha and beta diversity were assessed as well as the relative abundance of the most abundant bacterial and fungal taxa. The effects of covariates including disease activity and immunosuppressive therapies on microbial composition were evaluated.

Results Compared with controls, participants with GPA had a significantly different microbial composition (weighted UniFrac p=0.04) and lower relative abundance of Propionibacterium acnes and Staphylococcus epidermidis (for both, false discovery rate-corrected p=0.02). Disease activity in GPA was associated with a lower abundance of fungal order Malasseziales compared with participants with GPA in remission (p=0.04) and controls (p=0.01). Use of non-glucocorticoid immunosuppressive therapy was associated with ‘healthy’ nasal microbiota while participants with GPA who were off immunosuppressive therapy had more dysbiosis (weighted UniFrac p=0.01). No difference in the relative abundance of Staphylococcus aureus was observed between GPA and controls.

Conclusions GPA is associated with an altered nasal microbial composition, at both the bacterial and fungal levels. Use of immunosuppressive therapies and disease remission are associated with healthy microbial communities.

  • granulomatosis with polyangiitis
  • disease activity
  • infections

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Footnotes

  • Handling editor Josef S Smolen

  • Funding This work was supported by the CHOP Microbiome Center, the sequencing core of the PennCHOP Microbiome Center, and by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award K23-AR071514.

  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Institutional Review Board of the University of Pennsylvania.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement All sequence data related to this study are available from the United States National Center for Biotechnology Information (NCBI) Sequence Read Archive under accession number SRP149341.