Abstract
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.