Dataset Information

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

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-? 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, T_H1 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.

SUBMITTER: Cope EK

PROVIDER: S-EPMC5427582 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Publications

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

Cope Emily K EK Goldberg Andrew N AN Pletcher Steven D SD Lynch Susan V SV

Microbiome 20170512 1

<h4>Background</h4>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.<h4>Results</h4>Sinus brushings from patients with CRS (n = 59) and hea ...[more]

PMID: 28494786

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Project description:Background: Rabbits are useful for preclinical studies of sinusitis because of similar physiologic features to humans. The objective of this study is to develop a rabbit model of sinusitis that permits assessment of microanatomy and sampling for evaluating shifts in the sinus microbiota during the development of sinusitis and to test how the mucociliary clearance (MCC) defect might lead to dysbiosis and chronic rhinosinusitis (CRS). Methods: Generation of CRS was accomplished with an insertion of a sterile sponge into the left middle meatus of New Zealand white rabbits (n = 9) for 2 weeks. After sponge removal, 4 rabbits were observed for another 10 weeks and evaluated for CRS using endoscopy, microCT, visualization of the functional micro-anatomy by micro-optical coherence tomography (μOCT), and histopathological analysis of the sinus mucosa. Samples were taken from the left middle meatus and submitted for microbiome analysis. Results: CT demonstrated opacification of all left sinuses at 2 weeks in all rabbits (n = 9), which persisted in animals followed for another 12 weeks (n = 4). Histology at week 2 showed mostly neutrophils. On week 14, significant infiltration of plasma cells and lymphocytes was noted with increased submucosal glands compared to controls (p = 0.02). Functional microanatomy at 2 weeks showed diminished periciliary layer (PCL) depth (p < 0.0001) and mucus transport (p = 0.0044) compared to controls despite a thick mucus layer. By 12 weeks, the thickened mucus layer was resolved but PCL depletion persisted in addition to decreased ciliary beat frequency (CBF; p < 0.0001). The mucin fermenting microbes (Lactobacillales, Bacteroidales) dominated on week 2 and there was a significant shift to potential pathogens (e.g., Pseudomonas, Burkholderia) by week 14 compared to both controls and the acute phase (p < 0.05). Conclusion: We anticipate this reproducible model will provide a means for identifying underlying mechanisms of airway-surface liquid (ASL) depletion and fundamental changes in sinus microbial communities that contribute to the development of CRS. The rabbit model of sinusitis exhibited diminished PCL depth with delayed mucus transport and significant alterations and shift in the sinus microbiome during the development of chronic inflammation.

Project description:BackgroundThe sinus lift (or sinus augmentation) is a common procedure to improve maxillary bone stock before dental implantation. Chronic rhinosinusitis (CRS) is a potential complication of this procedure and may be refractory to medical treatment. Functional endoscopic sinus surgery has previously been used to address CRS, however, results of previous studies indicated that implant removal is required. There are limited follow-up data available.ObjectiveThe purpose of this study was to characterize the long-term outcomes and efficacy of endoscopic sinus surgery for refractory CRS after sinus lift, including the ability to salvage dental implants.MethodsThis was a retrospective case series that described nine patients who, between June 2011 and September 2016, underwent endoscopic sinus surgery for CRS after a sinus lift procedure. The presenting symptoms of the patients, medical management, imaging results, operative procedures, and outcomes were reviewed.ResultsThe majority of patients developed symptoms (mucopurulent nasal drainage, facial pain and/or pressure, nasal congestion, and foul smell) within 3 months of implant placement and were treated with at least three courses of antibiotics before referral to an otolaryngologist. All the patients underwent wide endoscopic maxillary antrostomy, with no surgical complications or postoperative reports of infection. There was a statistically significant improvement in 22-item Sino-Nasal Outcome Test scores (t(8) = -2.908; p = 0.02) and discharge, inflammation, and polyps/edema endoscopic scores ([z = -2.539; p = 0.011) between pre- and postsurgical treatment. Four patients had their dental implants removed before presentation. Among the five patients who presented with intact dental implants, none required removal before or after functional endoscopic sinus surgery.ConclusionFunctional endoscopic sinus surgery was a reasonable and efficacious treatment option for patients who presented with paranasal sinus disease after a sinus lift. Dental implant removal may not be a requirement for successful treatment of CRS associated with sinus lift procedures.

Dataset Information

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

Background

Results

Conclusions

Publications

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

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