Exploring the Role of Inflammation and Metabolites in Bell's Palsy and Potential Treatment Strategies

Introduction: Bell's palsy is a common acute peripheral neurological disorder causing unilateral facial paralysis. Its exact etiology remains unknown, but it is linked to inflammation, immune responses, infections, and ischemia. This study explores the potential causal relationship between Bell's palsy and peripheral blood inflammatory proteins, metabolites, and immune cell characteristics. Methods: Genetic data for Bell's palsy were obtained from the Finnish database (version R10) and IEU OpenGWAS. A two-sample Mendelian randomization (MR) approach was applied, analyzing 4907 plasma proteins, 731 immune cell traits, 91 inflammatory proteins, and 1400 metabolites. The Finnish dataset served as the discovery cohort, while the IEU OpenGWAS dataset acted as the validation cohort. Bioinformatics analyses included protein-protein interaction (PPI) networks, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, colocalization, and Linkage Disequilibrium Score Regression (LDSC) to identify candidate proteins and explore potential therapeutic targets. Results: MR analysis identified 70 inflammatory proteins, 77 metabolites, and 26 immune cell traits as potentially causally associated with Bell's palsy. After external validation, BLVRB, HMOX2, TNFRSF12A, DEFB128, ITM2A, VEGF-A, and DDX58 remained significantly associated (p < 0.05). PPI network analysis led to 31 candidate proteins, and six core proteins (JAK2, IL27RA, OSM, CCL19, SELL, VCAM-1) were identified. Conclusions: Our study identifies causal relationships between inflammatory proteins, metabolites, immune cells, and Bell's palsy, highlighting that the JAK/STAT signaling pathway may be a potentially critical target for intervention in Bell's palsy, and that its modulation may provide new directions and opportunities for therapeutic strategies and drug discovery for the disease.