Gut Microbiota Metabolites and Key Target Molecules in Allergic Rhinitis: A Multi-Omics Study of Gut-Nose Axis Regulation via the Inflammation-Metabolism Network

Jingqi Zhang^1,2Mengqi Zhao¹Ya Yu¹Yining Zeng¹Meiyi Sun¹Chuanyu Wu¹Tao Guo¹Liping Lin¹Zhiqing Liu²Hui Xie^2*

• ¹Chengdu University of Traditional Chinese Medicine, Chengdu, China
• ²Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China

Allergic rhinitis (AR) is an immune-mediated disorder with a steadily rising global prevalence. While emerging evidence suggests that gut microbiota and their metabolites can influence AR through immunoregulatory mechanisms, the specific molecular networks and key targets involved in this "gut-nasal axis" remain poorly defined. This study aims to explore potential associations between gut microbiota-derived metabolites and AR at a multi-level molecular network level, and to identify potential therapeutic targets for further investigation.Through an integrative multi-omics analysis of databases including gutMGene and GeneCards, we identified 20 overlapping genes associated with both AR and gut microbiota metabolites. This analysis suggested a significant genetic association between AR and core inflammatory mediators such as IL6, TNF, IL1B, and IL4R. Summary-data-based Mendelian randomization (SMR) analysis indicated that genetic variation, DNA methylation, and gene expression regulation within the interleukin gene family are closely associated with AR. Furthermore, single-cell analysis revealed distinct expression patterns of these core genes in the AR nasal mucosa. Upstream analysis highlighted a close relationship between AR and specific microbiota-derived metabolites, notably indole-3-propionic acid and succinate. Through target prediction and molecular docking, MPO and PTGDR2 were identified as potential key targets, while Fevipiprant and Zileuton were proposed as potential candidate drugs.This study provides an initial systematic exploration of the "gut-nasal" metabolic axis in AR, offering novel perspectives on the potential molecular links underlying the disease. The identified targets and candidate drugs provide a valuable list of candidates for developing novel therapeutic strategies and warrant further experimental validation for potential clinical translation.