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Spatial variability of the microbiome in chronic rhinosinusitis is associated with the patients’ clinical characteristics but not with sinus ostia occlusion

ABSTRACT: Spatial variability of the microbiome in chronic rhinosinusitis

PROVIDER: PRJEB55924 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR10221100_1.fastq.gz	Fastqsanger.gz
	ERR10221100_2.fastq.gz	Fastqsanger.gz
	ERR10221200_1.fastq.gz	Fastqsanger.gz
	ERR10221200_2.fastq.gz	Fastqsanger.gz
	ERR10221101_1.fastq.gz	Fastqsanger.gz

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Sinus bacterial communities in chronic rhinosinusitis

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Project description:Our data demonstrates an increased number of submucosal glands in the sinus mucosa of pediatric patients with chronic rhinosinusitis (CRS). Additionally, data in the literature indicates differentially altered expression of innate markers of immunity and of inflammatory mediators in the sinus mucosa of adult patients with cystic fibrosis, non-CF controls, and controls. Experiment Overall Design: Analyses will focus on inflammatory/immune response genes to identify genes in CRS or CF patients that are involved in pathways that impact on pathogenesis in these diseases. Analysis will also focus on genes in developmental pathways to identify mediators implicated in the development of submucosal glandular hyperplasia in pediatric patients with CRS.

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Project description:Persistent mucosal inflammation and microbial infection are characteristic of Chronic Rhinosinusitis (CRS). Though mucosal microbiota dysbiosis is a characteristic feature of other chronic inflammatory diseases, the relationship between sinus microbiota composition and CRS is unknown. Here we demonstrate, using comparative microbiome profiling of a cohort of CRS patients and healthy subjects, that the sinus microbiota of CRS patients exhibit significantly reduced bacterial diversity. Characteristic of this community collapse is the depletion of multiple, phylogenetically distinct, Lactic Acid Bacteria and the concomitant increase in relative abundance of a single species, Corynebacterium tuberculostearicum. Recapitulating the conditions observed in our human cohort in a murine model confirmed the pathogenic potential of C. tuberculostearicum and the critical necessity for a replete mucosal microbiota to protect against this species. Moreover, we provide evidence that Lactobacillus sakei, identified from our comparative microbiome analyses as a potentially protective species, affords defense against C. tuberculostearicum sinus infection, even in the context of a depleted sinus bacterial community. These studies demonstrate that sinus mucosal health is highly dependent on the composition of the resident microbiota, and identifies a new sino-pathogen and a strong bacterial candidate for therapeutic intervention.

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Project description:The study should create data for the selection of a clinically relevant primary endpoint to assess the efficacy and safety of Buparid/PARI SINUS as compared to Budes Nasal Spray in the therapy of chronic rhinosinusitis (CRS) with polyposis nasi in adult patients. Ideally, the selected parameter should allow a correlation between an objective methodology and the clinical outcome of the study patients.

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Project description:Asthmatic chronic rhinosinusitis with nasal polyps (aCRSwNP) is a common disruptive eosinophilic disease. Therefore, we sought to identify gene expression changes in nasosinus inflamed mucosa and adjacent polyp tissue from subjects with aCRSwNP. Twelve asthmatic chronic rhinosinusitis (aCRS) subjects (11 with nasal polyps; aCRSwNP) provided inflamed nasosinus mucosa (11 samples) and adjacent polyp (10 samples) or a small mixed mucosa and polyp specimen (1 sample) (thus, 22 samples overall). Inflamed mucosa or polyp was from the middle meatus or anterior ethmoid cavity. As control samples, nasosinus tissue was collected from the inferior turbinate or uncinate process from normal or rhinitis subjects without nasal polyps (n=17); 4 had physician-diagnosed allergic rhinitis (AR), 2 had suspected AR, 1 had suspected vasomotor rhinitis, and 10 had no signs of nasosinus disease, allergy, or atopy. All 4 AR subjects chose to donate tissue outside of their known allergy season(s).

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