Changes in the composition of the upper respiratory tract microbial community in granulomatosis with polyangiitis

Dysbiosis ̧ i.e. changes in microbial composition at a mucosal interface, is implicated in the pathogenesis of manychronic inflammatory and autoimmune diseases. To assess the composition of the microbial upper respiratory tract(URT) community in patients with granulomatosis with polyangiitis (GPA), we used culture-independent high-throughput methods. In this prospective clinical study, nasal swabs were collected from patients with GPA, patientswith rheumatoid arthritis (RA, disease control), and healthy controls. Nasal bacterial taxa were assessed using V3–V4region 16S rRNA amplicon sequencing. Staphylococcus aureus, Haemophilus influenza, and entero- and rhinoviruseswere detected using qPCR. Unbiased metagenomic RNA sequencing (UMERS) was performed in a subset of samplesto determine the relative abundance of bacterial, fungal, and viral species. A trend toward reduced microbiomediversity was detected in GPA samples compared with healthy controls. The abundance of bacterial taxa and microbialrichness were significantly decreased in GPA samples compared with RA samples. The relative abundance ofbacterial families shifted, with increased Planococcaceae and decreased Moraxellaceae, Tissierellaceae,Staphylococcaceae, and Propionibacteriaceae in GPA and RA. Further, decreased abundance of Corynebacteriaceae,and Aerococcaceae was observed in GPA samples. Significantly more colonization of S. aureus was seen in the nasalmicrobiome of GPA compared with RA and healthy control samples. H. influenzae colonization was also observed inGPA samples. UMERS detected the presence of rhinoviral sequences in some GPA samples. Thus, our studyuncovered changes in the URT microbial composition in patients with GPA and RA, suggesting that bothimmunosuppression and disease background affect the URT microbiome. Complex alterations of host-microbiomeinteractions in the URT could influence chronic endonasal inflammation in GPA.