Comparison of Subtyping Approaches and the Underlying Drivers of Microbial Signatures for Chronic Rhinosinusitis

ABSTRACT Chronic rhinosinusitis (CRS) is a heterogeneous condition characterized by persistent sinus inflammation and microbial dysbiosis. This study aimed to identify clinically relevant subgroups of CRS patients based on distinct microbial signatures, with a comparison to the commonly used phenoty...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Kristi Biswas, Raewyn Cavubati, Shan Gunaratna, Michael Hoggard, Sharon Waldvogel-Thurlow, Jiwon Hong, Kevin Chang, Brett Wagner Mackenzie, Michael W. Taylor, Richard G. Douglas
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	epithelial barrier microbiota tight junctions inflammation mucosal integrity sinusitis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/eb99cd9cf99e4375924994efef2cf38c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:eb99cd9cf99e4375924994efef2cf38c
record_format	dspace
spelling	oai:doaj.org-article:eb99cd9cf99e4375924994efef2cf38c2021-11-15T15:22:04ZComparison of Subtyping Approaches and the Underlying Drivers of Microbial Signatures for Chronic Rhinosinusitis10.1128/mSphere.00679-182379-5042https://doaj.org/article/eb99cd9cf99e4375924994efef2cf38c2019-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00679-18https://doaj.org/toc/2379-5042ABSTRACT Chronic rhinosinusitis (CRS) is a heterogeneous condition characterized by persistent sinus inflammation and microbial dysbiosis. This study aimed to identify clinically relevant subgroups of CRS patients based on distinct microbial signatures, with a comparison to the commonly used phenotypic subgrouping approach. The underlying drivers of these distinct microbial clusters were also investigated, together with associations with epithelial barrier integrity. Sinus biopsy specimens were collected from CRS patients (n = 23) and disease controls (n = 8). The expression of 42 tight junction genes was evaluated using quantitative PCR together with microbiota analysis and immunohistochemistry for measuring mucosal integrity and inflammation. CRS patients clustered into two distinct microbial subgroups using probabilistic modelling Dirichlet (DC) multinomial mixtures. DC1 exhibited significantly reduced bacterial diversity and increased dispersion and was dominated by Pseudomonas, Haemophilus, and Achromobacter. DC2 had significantly elevated B cells and incidences of nasal polyps and higher numbers of Anaerococcus, Megasphaera, Prevotella, Atopobium, and Propionibacterium. In addition, each DC exhibited distinct tight junction gene and protein expression profiles compared with those of controls. Stratifying CRS patients based on clinical phenotypic subtypes (absence or presence of nasal polyps [CRSsNP or CRSwNP, respectively] or with cystic fibrosis [CRSwCF]) accounted for a larger proportion of the variation in the microbial data set than with DC groupings. However, no significant differences between CRSsNP and CRSwNP cohorts were observed for inflammatory markers, beta-dispersion, and alpha-diversity measures. In conclusion, both approaches used for stratifying CRS patients had benefits and pitfalls, but DC clustering provided greater resolution when studying tight junction impairment. Future studies in CRS should give careful consideration to the patient subtyping approach used. IMPORTANCE Chronic rhinosinusitis (CRS) is a major human health problem that significantly reduces quality of life. While various microbes have been implicated, there is no clear understanding of the role they play in CRS pathogenesis. Another equally important observation made for CRS patients is that the epithelial barrier in the sinonasal cavity is defective. Finding a robust approach to subtype CRS patients would be the first step toward unravelling the pathogenesis of this heterogeneous condition. Previous work has explored stratification based on the clinical presentation of the disease (with or without polyps), inflammatory markers, pathology, or microbial composition. Comparisons between the different stratification approaches used in these studies have not been possible due to the different cohorts, analytical methods, or sample sites used. In this study, two approaches for subtyping CRS patients were compared, and the underlying drivers of the heterogeneity in CRS were also explored.Kristi BiswasRaewyn CavubatiShan GunaratnaMichael HoggardSharon Waldvogel-ThurlowJiwon HongKevin ChangBrett Wagner MackenzieMichael W. TaylorRichard G. DouglasAmerican Society for Microbiologyarticleepithelial barriermicrobiotatight junctionsinflammationmucosal integritysinusitisMicrobiologyQR1-502ENmSphere, Vol 4, Iss 1 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	epithelial barrier microbiota tight junctions inflammation mucosal integrity sinusitis Microbiology QR1-502
spellingShingle	epithelial barrier microbiota tight junctions inflammation mucosal integrity sinusitis Microbiology QR1-502 Kristi Biswas Raewyn Cavubati Shan Gunaratna Michael Hoggard Sharon Waldvogel-Thurlow Jiwon Hong Kevin Chang Brett Wagner Mackenzie Michael W. Taylor Richard G. Douglas Comparison of Subtyping Approaches and the Underlying Drivers of Microbial Signatures for Chronic Rhinosinusitis
description	ABSTRACT Chronic rhinosinusitis (CRS) is a heterogeneous condition characterized by persistent sinus inflammation and microbial dysbiosis. This study aimed to identify clinically relevant subgroups of CRS patients based on distinct microbial signatures, with a comparison to the commonly used phenotypic subgrouping approach. The underlying drivers of these distinct microbial clusters were also investigated, together with associations with epithelial barrier integrity. Sinus biopsy specimens were collected from CRS patients (n = 23) and disease controls (n = 8). The expression of 42 tight junction genes was evaluated using quantitative PCR together with microbiota analysis and immunohistochemistry for measuring mucosal integrity and inflammation. CRS patients clustered into two distinct microbial subgroups using probabilistic modelling Dirichlet (DC) multinomial mixtures. DC1 exhibited significantly reduced bacterial diversity and increased dispersion and was dominated by Pseudomonas, Haemophilus, and Achromobacter. DC2 had significantly elevated B cells and incidences of nasal polyps and higher numbers of Anaerococcus, Megasphaera, Prevotella, Atopobium, and Propionibacterium. In addition, each DC exhibited distinct tight junction gene and protein expression profiles compared with those of controls. Stratifying CRS patients based on clinical phenotypic subtypes (absence or presence of nasal polyps [CRSsNP or CRSwNP, respectively] or with cystic fibrosis [CRSwCF]) accounted for a larger proportion of the variation in the microbial data set than with DC groupings. However, no significant differences between CRSsNP and CRSwNP cohorts were observed for inflammatory markers, beta-dispersion, and alpha-diversity measures. In conclusion, both approaches used for stratifying CRS patients had benefits and pitfalls, but DC clustering provided greater resolution when studying tight junction impairment. Future studies in CRS should give careful consideration to the patient subtyping approach used. IMPORTANCE Chronic rhinosinusitis (CRS) is a major human health problem that significantly reduces quality of life. While various microbes have been implicated, there is no clear understanding of the role they play in CRS pathogenesis. Another equally important observation made for CRS patients is that the epithelial barrier in the sinonasal cavity is defective. Finding a robust approach to subtype CRS patients would be the first step toward unravelling the pathogenesis of this heterogeneous condition. Previous work has explored stratification based on the clinical presentation of the disease (with or without polyps), inflammatory markers, pathology, or microbial composition. Comparisons between the different stratification approaches used in these studies have not been possible due to the different cohorts, analytical methods, or sample sites used. In this study, two approaches for subtyping CRS patients were compared, and the underlying drivers of the heterogeneity in CRS were also explored.
format	article
author	Kristi Biswas Raewyn Cavubati Shan Gunaratna Michael Hoggard Sharon Waldvogel-Thurlow Jiwon Hong Kevin Chang Brett Wagner Mackenzie Michael W. Taylor Richard G. Douglas
author_facet	Kristi Biswas Raewyn Cavubati Shan Gunaratna Michael Hoggard Sharon Waldvogel-Thurlow Jiwon Hong Kevin Chang Brett Wagner Mackenzie Michael W. Taylor Richard G. Douglas
author_sort	Kristi Biswas
title	Comparison of Subtyping Approaches and the Underlying Drivers of Microbial Signatures for Chronic Rhinosinusitis
title_short	Comparison of Subtyping Approaches and the Underlying Drivers of Microbial Signatures for Chronic Rhinosinusitis
title_full	Comparison of Subtyping Approaches and the Underlying Drivers of Microbial Signatures for Chronic Rhinosinusitis
title_fullStr	Comparison of Subtyping Approaches and the Underlying Drivers of Microbial Signatures for Chronic Rhinosinusitis
title_full_unstemmed	Comparison of Subtyping Approaches and the Underlying Drivers of Microbial Signatures for Chronic Rhinosinusitis
title_sort	comparison of subtyping approaches and the underlying drivers of microbial signatures for chronic rhinosinusitis
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/eb99cd9cf99e4375924994efef2cf38c
work_keys_str_mv	AT kristibiswas comparisonofsubtypingapproachesandtheunderlyingdriversofmicrobialsignaturesforchronicrhinosinusitis AT raewyncavubati comparisonofsubtypingapproachesandtheunderlyingdriversofmicrobialsignaturesforchronicrhinosinusitis AT shangunaratna comparisonofsubtypingapproachesandtheunderlyingdriversofmicrobialsignaturesforchronicrhinosinusitis AT michaelhoggard comparisonofsubtypingapproachesandtheunderlyingdriversofmicrobialsignaturesforchronicrhinosinusitis AT sharonwaldvogelthurlow comparisonofsubtypingapproachesandtheunderlyingdriversofmicrobialsignaturesforchronicrhinosinusitis AT jiwonhong comparisonofsubtypingapproachesandtheunderlyingdriversofmicrobialsignaturesforchronicrhinosinusitis AT kevinchang comparisonofsubtypingapproachesandtheunderlyingdriversofmicrobialsignaturesforchronicrhinosinusitis AT brettwagnermackenzie comparisonofsubtypingapproachesandtheunderlyingdriversofmicrobialsignaturesforchronicrhinosinusitis AT michaelwtaylor comparisonofsubtypingapproachesandtheunderlyingdriversofmicrobialsignaturesforchronicrhinosinusitis AT richardgdouglas comparisonofsubtypingapproachesandtheunderlyingdriversofmicrobialsignaturesforchronicrhinosinusitis
_version_	1718428102730711040

Comparison of Subtyping Approaches and the Underlying Drivers of Microbial Signatures for Chronic Rhinosinusitis

Ejemplares similares