Biodiversity of the Bacterial and Fungal Microbiome and Associated Inflammatory Cytokine Profile in Chronic Rhinosinusitis

Abstract

Background: Dysbiosis of the bacterial and fungal microbiome has been increasingly implicated in the pathogenesis of chronic rhinosinusitis (CRS). This study explores the relationship between microbiome and mycobiome biodiversity and type 2 (T2) versus non-type 2 (NT2) inflammation. Methods: Mucosal tissues from the ethmoid sinus were collected during endoscopic sinus (CRS) and skull base (controls) surgery between January 2020 and July 2021. Specimens underwent 16S rRNA (bacterial) and internal transcribed spacer (fungal) gene sequencing, along with cytokine analysis using the Luminex assay. Based on cytokine (IL-4, IL-5, IL-13) concentrations and the presence of eosinophils, CRS cases were classified into T2 or NT2 inflammatory profiles. The relationships between CRS endotype and the biodiversity of the microbiome and mycobiome were assessed. Results: Specimens from 92 patients (30 control, 31 CRSwNP, 31 CRSsNP) were included in the analyses. Among 62 CRS cases, 20 exhibited T2 inflammation and 42 exhibited NT2 inflammation. Compared with control specimens, NT2 specimens exhibited significantly lower amplicon sequence variants (mean difference −149, 95% CI [−261, −37], p = 0.007), Shannon index (−0.48 [−0.79, −0.16], p = 0.002), and Simpson index (−0.003 [−0.005, −0.001], p = 0.002) for bacterial alpha diversity. However, no significant differences in bacterial alpha diversity were observed between T2 specimens and controls, or between T2 and NT2 specimens. Fungal biodiversity did not differ significantly across endotype and control groups. Conclusion: Dysbiosis of the sinus bacterial microbiome is more strongly associated with a NT2-mediated inflammatory profile than with a T2-mediated inflammatory profile.