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Microbiome. 2017 May 12;5(1):53. doi: 10.1186/s40168-017-0266-6.

Compositionally and functionally distinct sinus microbiota in chronic rhinosinusitis patients have immunological and clinically divergent consequences.

Author information

1
Department of Otolaryngology, University of California, San Francisco, CA, 94143, USA.
2
Present Address: Pathogen and Microbiome Institute, Northern Arizona University, Flagstaff, AZ, 86011, USA.
3
Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA, 94143, USA. Susan.Lynch@ucsf.edu.

Abstract

BACKGROUND:

Chronic rhinosinusitis (CRS) is a heterogeneous disease characterized by persistent sinonasal inflammation and sinus microbiome dysbiosis. The basis of this heterogeneity is poorly understood. We sought to address the hypothesis that a limited number of compositionally distinct pathogenic bacterial microbiota exist in CRS patients and invoke discrete immune responses and clinical phenotypes in CRS patients.

RESULTS:

Sinus brushings from patients with CRS (n = 59) and healthy individuals (n = 10) collected during endoscopic sinus surgery were analyzed using 16S rRNA gene sequencing, predicted metagenomics, and RNA profiling of the mucosal immune response. We show that CRS patients cluster into distinct sub-groups (DSI-III), each defined by specific pattern of bacterial co-colonization (permutational multivariate analysis of variance (PERMANOVA); p = 0.001, r 2 = 0.318). Each sub-group was typically dominated by a pathogenic family: Streptococcaceae (DSI), Pseudomonadaceae (DSII), Corynebacteriaceae [DSIII(a)], or Staphylococcaceae [DSIII(b)]. Each pathogenic microbiota was predicted to be functionally distinct (PERMANOVA; p = 0.005, r 2 = 0.217) and encode uniquely enriched gene pathways including ansamycin biosynthesis (DSI), tryptophan metabolism (DSII), two-component response [DSIII(b)], and the PPAR-γ signaling pathway [DSIII(a)]. Each is also associated with significantly distinct host immune responses; DSI, II, and III(b) invoked a variety of pro-inflammatory, TH1 responses, while DSIII(a), which exhibited significantly increased incidence of nasal polyps (Fisher's exact; p = 0.034, relative risk = 2.16), primarily induced IL-5 expression (Kruskal Wallis; q = 0.045).

CONCLUSIONS:

A large proportion of CRS patient heterogeneity may be explained by the composition of their sinus bacterial microbiota and related host immune response-features which may inform strategies for tailored therapy in this patient population.

KEYWORDS:

Airway; Chronic rhinosinusitis; Colonization patterns; Cystic fibrosis; Dirichlet state; Microbiome; Microbiota; Microbiota state; Predicted metagenome; Sinus

PMID:
28494786
PMCID:
PMC5427582
DOI:
10.1186/s40168-017-0266-6
[Indexed for MEDLINE]
Free PMC Article

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