The composition and functional protein subsystems of the human nasal microbiome in granulomatosis with polyangiitis: a pilot study
Abstract 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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-10-01
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| Series: | Microbiome |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s40168-019-0753-z |
| _version_ | 1818558265402851328 |
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| author | Josef Wagner Ewan M. Harrison Marcos Martinez Del Pero Beth Blane Gert Mayer Johannes Leierer Seerapani Gopaluni Mark A. Holmes Julian Parkhill Sharon J. Peacock David R. W. Jayne Andreas Kronbichler |
| author_facet | Josef Wagner Ewan M. Harrison Marcos Martinez Del Pero Beth Blane Gert Mayer Johannes Leierer Seerapani Gopaluni Mark A. Holmes Julian Parkhill Sharon J. Peacock David R. W. Jayne Andreas Kronbichler |
| author_sort | Josef Wagner |
| collection | DOAJ |
| description | Abstract 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 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. Results The 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. Conclusion Our 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. |
| first_indexed | 2024-12-14T00:10:22Z |
| format | Article |
| id | doaj.art-267567807e214569b56c28d0ff7572be |
| institution | Directory Open Access Journal |
| issn | 2049-2618 |
| language | English |
| last_indexed | 2024-12-14T00:10:22Z |
| publishDate | 2019-10-01 |
| publisher | BMC |
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| series | Microbiome |
| spelling | doaj.art-267567807e214569b56c28d0ff7572be2022-12-21T23:25:47ZengBMCMicrobiome2049-26182019-10-017111710.1186/s40168-019-0753-zThe composition and functional protein subsystems of the human nasal microbiome in granulomatosis with polyangiitis: a pilot studyJosef Wagner0Ewan M. Harrison1Marcos Martinez Del Pero2Beth Blane3Gert Mayer4Johannes Leierer5Seerapani Gopaluni6Mark A. Holmes7Julian Parkhill8Sharon J. Peacock9David R. W. Jayne10Andreas Kronbichler11Wellcome Sanger InstituteWellcome Sanger InstituteWest Suffolk HospitalDepartment of Medicine, University of CambridgeDepartment of Internal Medicine IV (Nephrology and Hypertension), Medical University InnsbruckDepartment of Internal Medicine IV (Nephrology and Hypertension), Medical University InnsbruckVasculitis and Lupus ClinicDepartment of Veterinary Medicine, University of CambridgeWellcome Sanger InstituteWellcome Sanger InstituteDepartment of Medicine, University of CambridgeDepartment of Internal Medicine IV (Nephrology and Hypertension), Medical University InnsbruckAbstract 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 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. Results The 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. Conclusion Our 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.http://link.springer.com/article/10.1186/s40168-019-0753-zGPAMicrobiomeANCAVasculitisStaphylococcusrRNA sequencing |
| spellingShingle | Josef Wagner Ewan M. Harrison Marcos Martinez Del Pero Beth Blane Gert Mayer Johannes Leierer Seerapani Gopaluni Mark A. Holmes Julian Parkhill Sharon J. Peacock David R. W. Jayne Andreas Kronbichler The composition and functional protein subsystems of the human nasal microbiome in granulomatosis with polyangiitis: a pilot study Microbiome GPA Microbiome ANCA Vasculitis Staphylococcus rRNA sequencing |
| title | The composition and functional protein subsystems of the human nasal microbiome in granulomatosis with polyangiitis: a pilot study |
| title_full | The composition and functional protein subsystems of the human nasal microbiome in granulomatosis with polyangiitis: a pilot study |
| title_fullStr | The composition and functional protein subsystems of the human nasal microbiome in granulomatosis with polyangiitis: a pilot study |
| title_full_unstemmed | The composition and functional protein subsystems of the human nasal microbiome in granulomatosis with polyangiitis: a pilot study |
| title_short | The composition and functional protein subsystems of the human nasal microbiome in granulomatosis with polyangiitis: a pilot study |
| title_sort | composition and functional protein subsystems of the human nasal microbiome in granulomatosis with polyangiitis a pilot study |
| topic | GPA Microbiome ANCA Vasculitis Staphylococcus rRNA sequencing |
| url | http://link.springer.com/article/10.1186/s40168-019-0753-z |
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