Dysbiosis of nasal microbiota associated with hippocampal neuroimmune alterations in a mouse model of eosinophilic chronic rhinosinusitis

Chronic rhinosinusitis (CRS) is a chronic inflammatory disease of the nasal cavity and paranasal sinuses. Eosinophilic CRS (ECRS) is a refractory subtype characterized by persistent type 2 inflammation. Epidemiological and animal studies suggest that CRS may affect brain function and that microbiota dysbiosis may contribute to the pathophysiology of CRS. However, the relationship between microbiota alterations and neuroimmune changes remains poorly understood in CRS. In this study, we investigated nasal and gut microbiota together with glial and inflammatory gene expression in the olfactory bulb (OB) and hippocampus in a mouse model of ECRS, and examined their associations. The nasal and cecal microbiota were analyzed by 16S rRNA gene amplicon sequencing, and glial and inflammatory gene expression in the OB and hippocampus was assessed by real-time RT-PCR. Associations between microbial taxa and brain gene expression were analyzed using MaAsLin2. While alpha diversity was unchanged, beta diversity of both nasal and gut microbiota differed significantly in ECRS mice. Differential abundance analyses identified several nasal and gut bacterial taxa altered in ECRS. In parallel, expression of glial markers was increased in the OB and hippocampus, and expression of the pro-inflammatory cytokine gene Il-6 was elevated in the hippocampus. Notably, multiple nasal microbial taxa, but not gut bacteria, were significantly associated with hippocampal glial and inflammatory gene expression. These findings indicate that ECRS is accompanied by dysbiosis of the nasal and gut microbiota together with hippocampal neuroimmune alterations and suggest a potential link between nasal microbiota composition and hippocampal neuroimmune alterations.