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

Abstract

BackgroundEar, 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 shotgun metagenomics in patients with active and inactive granulomatosis with polyangiitis (GPA). Shotgun 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.ResultsThe presence of S. aureus in the nose as assessed by culture was more frequently detected in patients with active GPA (66.7%) compared with inactive GPA (34.1%). Beta diversity analysis of nasal microbiota by bacterial 16S rRNA profiling revealed a different composition between GPA patients and healthy controls (P = 0.039). Beta diversity analysis of shotgun metagenomic sequence data for Staphylococcus spp. revealed a different composition between active GPA patients and healthy controls and disease controls (P = 0.0007 and P = 0.0023, respectively), and between healthy controls and 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.ConclusionOur data revealed a distinct dysbiosis of the nasal microbiota in GPA patients compared with disease and healthy 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.

Updates in antineutrophil cytoplasmic antibody (ANCA)‐associated vasculitis for the ENT surgeon

“…GWAS has also indicated that EGPA may be two distinct diseases based on ANCA status, with ANCA negative disease distinct from AAV. Metagenomic sequencing of nasal swabs has confirmed an association between nasal microbiome dysbiosis and disease activity in GPA; disease activity is associated with S aureus predominance, compared with S epidermidis in quiescent disease and controls 89 . High lifetime silica exposure has been associated with an increased risk of developing AAV 90 which, combined with the typical early respiratory tract involvement, raises of the possibility of other inhaled environmental triggers in the disease.…”

“…Metagenomic sequencing of nasal swabs has confirmed an association between nasal microbiome dysbiosis and disease activity in GPA; disease activity is associated with S aureus predominance, compared with S epidermidis in quiescent disease and controls. 89 High lifetime silica exposure has been associated with an increased risk of developing AAV 90 in EGPA. Rituximab is replacing conventional therapy as both a remission-induction and maintenance agent [92][93][94][95] and has also shown benefit in the specific management of head and neck manifestations of GPA.…”

Nasal microbiome research in ANCA-associated vasculitis: Strengths, limitations, and future directions

“…Esp-secreting S. epidermidis correlates with the absence of S. aureus [36] or secretion of hydrogen peroxide by Streptococcus pneumoniae [37] ), whereas indirect competition may be related to modified living conditions or competition for nutrients [38] . In our pilot study investigating the nasal microbiome in patients with GPA, we found that in most cases with presence of Staphylococcus pseudintermedius the antagonistic relationship between S. aureus and S. epidermidis is broken, indicating that all three occupy the same niche [39] .…”

Characterization and Analysis of The Nasal Microbiota and Plasmatic Extracellular Vesicles in Allergic Rhinitis: A Case-Control Study

“…Indeed, the AR patients' bNM was less rich in terms of residential bacteria and associated with a reduced bacterial phylogenetic diversity compared to the HS group. Interestingly, reduced diversity in the bNM was identi ed also in other respiratory diseases such as in patients with Chronic Rhinosinusitis (CRS) [56,57], in patients with asthma [58], and in patients affected by granulomatosis with polyangiitis [59]. The importance of a diverse microbiota has been widely documented as pivotal in maintaining the mucosa integrity and an effective immune system [16,45,60].…”