Dupilumab Treatment Is Associated With Clinical Improvement and a Shift Toward a Health-Associated Nasal Passage Microbiota in Diffuse Type 2 Chronic Rhinosinusitis.

Abstract

Background Nasal microbiota composition of patients with diffuse type 2 chronic rhinosinusitis with nasal polyps (CRSwNP) is altered compared to healthy individuals. Dupilumab, an anti-IL-4Rα-mAb, modulates type 2 inflammation, but the effect on microbiota composition in CRSwNP is unknown. The aim of this study was to investigate longitudinal effects of dupilumab on the nasal passage and gastrointestinal microbiota in patients with diffuse type 2 CRSwNP.Methods Twenty-seven patients with diffuse type 2 CRSwNP treated with dupilumab 300 mg subcutaneously every 2 weeks, 10 untreated patients with CRSwNP, and 11 healthy controls were included. Nasal and stool samples were collected at Days 0, 28, 90, and 180 posttreatment of the treated CRSwNP group and at Days 0 and 28 of untreated CRSwNP and healthy controls. The samples were analyzed using 16S rRNA gene amplicon sequencing (V3/V4).Results In CRSwNP patients, the most abundant genera in nasal passage microbiota were Corynebacterium and Staphylococcus. Cutibacterium and Lawsonella were less abundant in CRSwNP at baseline compared to healthy controls. Dupilumab treatment was associated with increased relative abundances in the nasal passage of genera such as Lawsonella, Corynebacterium, and Dolosigranulum. Microbial diversity of the gastrointestinal microbiota in CRSwNP at baseline was significantly higher than in healthy controls. There were no changes in gastrointestinal microbiota during dupilumab treatment.Conclusion Dupilumab treatment was associated with a shift in the nasal passage bacterial microbiota toward that of healthy controls, whereas the composition of gastrointestinal microbiota did not change. These findings suggest that nasal passage microbiota composition is influenced by the underlying inflammatory endotype.