Dynamic Changes in the Nasal Microbiome Associated With Disease Activity in Patients With Granulomatosis With Polyangiitis

• Published in: Arthritis & rheumatology (Hoboken, N.J.) Vol. 73; no. 9; pp. 1703 - 1712
• Main Authors: Rhee, Rennie L., Lu, Jiarui, Bittinger, Kyle, Lee, Jung‐Jin, Mattei, Lisa M., Sreih, Antoine G., Chou, Sherry, Miner, Jonathan J., Cohen, Noam A., Kelly, Brendan J., Lee, Hongzhe, Grayson, Peter C., Collman, Ronald G., Merkel, Peter A.
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-09-2021
• Subjects: Abundance; Adult; Antibodies; Antineutrophil cytoplasmic antibodies; Bacteria; Corynebacterium; Corynebacterium - isolation & purification; Female; Gene sequencing; Granulomatosis; Granulomatosis with Polyangiitis - microbiology; Humans; Inflammatory diseases; Male; Microbiomes; Microbiota; Middle Aged; Nasal Cavity - microbiology; Proteinase; Proteinase 3; Relative abundance; Remission; rRNA 16S; Staphylococcus; Staphylococcus - isolation & purification; Vein & artery diseases
• ISSN: 2326-5191; 2326-5205
• DOI: 10.1002/art.41723

Objective
Little is known about temporal changes in nasal bacteria in granulomatosis with polyangiitis (GPA). This study was undertaken to examine longitudinal changes in the nasal microbiome in association with relapse in GPA patients.
Methods
Bacterial 16S ribosomal RNA gene sequencing was performed on nasal swabs from 19 patients with GPA who were followed up longitudinally for a total of 78 visits, including 9 patients who experienced a relapse and 10 patients who remained in remission. Relative abundance of bacteria and ratios between bacteria were examined. Generalized estimating equation models were used to evaluate the association between bacterial composition and 1) disease activity and 2) levels of antineutrophil cytoplasmic antibody (ANCA) with specificity for proteinase 3 (PR3), adjusted for medication.
Results
Corynebacterium and Staphylococcus were the most abundant bacterial genera across all nasal samples. Patients with quiescent disease maintained a stable ratio of Corynebacterium to Staphylococcus across visits. In contrast, in patients who experienced a relapse, a significantly lower ratio was observed at the visit prior to relapse, followed by a higher ratio at the time of relapse (adjusted P < 0.01). Species‐level analysis identified an association between a higher abundance of nasal Corynebacterium tuberculostearicum and 1) relapse (adjusted P = 0.04) and 2) higher PR3‐ANCA levels (adjusted P = 0.02).
Conclusion
In GPA, significant changes occur in the nasal microbiome over time and are associated with disease activity. The occurrence of these changes months prior to the onset of relapse supports a pathogenic role of nasal bacteria in GPA. Our results uphold existing hypotheses implicating Staphylococcus as an instigator of disease and have generated a novel finding involving Corynebacterium as a potential mediator of disease in GPA.