嗜酸性慢性鼻窦炎小鼠模型中鼻腔微生物群失调与海马神经免疫改变相关

文献信息

中文摘要

慢性鼻窦炎（CRS）是鼻腔和鼻窦的慢性炎症性疾病。嗜酸性CRS（ECRS）是一种以持续性2型炎症为特征的难治性亚型。流行病学和动物研究表明，CRS可能影响脑功能，且微生物群失调可能参与CRS的病理生理过程。然而，在CRS中，微生物群改变与神经免疫变化之间的关系仍知之甚少。在本研究中，我们调查了ECRS小鼠模型中鼻腔和肠道微生物群以及嗅球（OB）和海马中胶质细胞和炎症基因表达，并检查了它们之间的关联。通过16S rRNA基因扩增子测序分析鼻腔和盲肠微生物群，并通过实时RT-PCR评估OB和海马中胶质细胞和炎症基因表达。使用MaAsLin2分析微生物分类群与脑基因表达之间的关联。虽然α多样性未改变，但ECRS小鼠鼻腔和肠道微生物群的β多样性均存在显著差异。差异丰度分析鉴定出几种在ECRS中改变的鼻腔和肠道细菌分类群。同时，OB和海马中胶质细胞标志物的表达增加，海马中促炎细胞因子基因Il-6的表达升高。值得注意的是，多种鼻腔微生物分类群，而非肠道细菌，与海马胶质细胞和炎症基因表达显著相关。这些发现表明，ECRS伴随鼻腔和肠道微生物群失调以及海马神经免疫改变，并提示鼻腔微生物群组成与海马神经免疫改变之间可能存在联系。

英文摘要

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.