Abstract

Dysbiosis of the sinus microbiome affects the pathophysiology of chronic rhinosinusitis with nasal polyps (CRSwNPs). We investigated whether the sinus microbiota in CRSwNPs is associated with eosinophilic inflammation, especially in relation to innate lymphoid cells (ILCs), prognosis, and serum extracellular vesicles (EVs). Middle meatal swabs and serum from 31 CRSwNPs patients and six healthy controls were analyzed by 16S ribosomal RNA sequencing. ILC2s and cytokines from sinonasal tissues were measured by flow cytometry and ELISA, respectively. The relative abundances (RAs) of bacteria were compared based on eosinophilic inflammation and surgical outcome. The correlations between sinus bacteria and ILC2s, cytokines, and serum EVs were analyzed. The compositions of sinus bacteria were different between groups at the genus level. In eosinophilic CRSwNPs patients, the RA of Anaerococcus was significantly decreased (P = 0.010), whereas that of Lachnoclostridium was significantly increased (P = 0.038) compared with that in controls. The RA of Lachnoclostridium showed a significant positive correlation with interleukin (IL)-5-producing ILC2 populations (R = 0.340, P = 0.049), whereas the RA of Anaerococcus showed a negative correlation with IL-5-producing ILC2 populations (R = −0.332, P = 0.055). The RAs of Corynebacterium, Anaerococcus, and Tepidimonas were significantly decreased in patients with suboptimal outcomes compared with those in patients with optimal outcomes and control subjects. Some sinus bacteria and serum EVs showed positive correlations. CRSwNPs patients showed distinct microbiota compositions based on eosinophilic inflammation in relation to ILC2s and surgical outcome. These findings support a relationship between the microbiota and the host immune response in CRSwNPs.

Highlights

  • Chronic rhinosinusitis (CRS) is a multifactorial chronic upper airway inflammatory disease

  • Sinus bacteria did not differ at the phylum level between control subjects, eosinophilic CRS with nasal polyps (CRSwNPs) patients, and noneosinophilic CRSwNPs patients (Fig. E1b)

  • Sinus bacterial compositions were different at the genus level among control subjects, eosinophilic CRSwNPs patients, and noneosinophilic CRSwNPs patients (Fig. 1a)

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Summary

Introduction

Chronic rhinosinusitis (CRS) is a multifactorial chronic upper airway inflammatory disease. Putative pathological factors include changes in the microbiota, an imbalance of the local or systemic immune system, allergens, toxins, and genetic predisposition[1,2,3]. Several studies have reported that the microbiota may affect the pathophysiology of CRS. A decrease in microbial diversity and an increase in the total number of microorganisms have been reported in patients with CRS4,5. Dysbiosis of the microbiota could be the driving force of CRS. Immunologic features associated with the nature or composition of the sinus microbiota could partially explain the heterogeneity of CRS. CRS with nasal polyps (CRSwNPs) is generally classified as eosinophilic or noneosinophilic, which show distinct immunological features. When a CRS patient cluster was divided into distinct subgroups according to the specific pattern of bacterial cocolonization, each subgroup was associated with a host immune response. Some subgroups exhibited increased expression of the interleukin 6, tumor necrosis factor, IL8, and IL10

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