Huang Junwei, Zhu Xiao, Yao Jingxin, Yang Weili, Zhu Zhenhua
The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan Province, China.
Hunan University of Chinese Medicine, Changsha, Hunan Province, China.
Medicine (Baltimore). 2025 Jan 17;104(3):e41093. doi: 10.1097/MD.0000000000041093.
Allergic rhinitis (AR) is a common allergic inflammatory disease that affects the upper respiratory tract. Although previous research suggests a potential association between gut microbiota alterations and AR, the causal relationship remains unclear. This study employs Mendelian randomization (MR) to reduce confounding factors and reverse causality. By using genetic variants as instrumental variables, the MR approach aims to provide more reliable causal evidence of the relationship between gut microbiota, immune-related antibodies, and AR. This study utilized large-scale genome-wide association study data from the FINRISK 2002 cohort and the UK Biobank to systematically investigate the causal relationships between gut microbiota, antibody immune responses, and AR through a 2-sample MR approach. We applied the inverse variance weighting method to assess the potential mediating role of antibody immune responses in the interaction between gut microbiota and AR. MR analysis identified 17 gut microbiomes significantly associated with chronic rhinosinusitis (CRS) risk. Specifically, increased abundances of the CAG-884 and UBA1407 species were linked to a higher CRS risk, while greater levels of Atopobiaceae and Bacteroides thetaiotaomicron were associated with a reduced risk. In addition, of the 29 immune cell types correlated with CRS, 12 were found to increase risk, while 17 reduced it. Notably, CAG-884 indirectly influenced CRS risk by affecting the proportion of TD double negative (CD4-CD8-) % T cells, with a mediating effect ratio of 36.4%. Our findings confirm a causal relationship between gut microbiota and immune cells in relation to CRS, underscoring the mediating role of immune cells in this interaction.
变应性鼻炎（AR）是一种影响上呼吸道的常见变应性炎症性疾病。尽管先前的研究表明肠道微生物群改变与AR之间存在潜在关联，但因果关系仍不明确。本研究采用孟德尔随机化（MR）方法以减少混杂因素并逆转因果关系。通过使用基因变异作为工具变量，MR方法旨在为肠道微生物群、免疫相关抗体与AR之间的关系提供更可靠的因果证据。本研究利用来自FINRISK 2002队列和英国生物银行的大规模全基因组关联研究数据，通过两样本MR方法系统地研究肠道微生物群、抗体免疫反应与AR之间的因果关系。我们应用逆方差加权法评估抗体免疫反应在肠道微生物群与AR相互作用中的潜在中介作用。MR分析确定了17种肠道微生物群与慢性鼻-鼻窦炎（CRS）风险显著相关。具体而言，CAG-884和UBA1407菌种丰度增加与较高的CRS风险相关，而阿托波菌科和嗜热栖热放线菌水平较高则与风险降低相关。此外，在与CRS相关的29种免疫细胞类型中，发现12种会增加风险，而17种会降低风险。值得注意的是，CAG-884通过影响TD双阴性（CD4-CD8-）% T细胞的比例间接影响CRS风险，中介效应比为36.4%。我们的研究结果证实了肠道微生物群与免疫细胞在CRS方面的因果关系，强调了免疫细胞在这种相互作用中的中介作用。
