Association between oral microbiota and inflammatory bowel disease: A 2-sample Mendelian randomization study in East...

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is increasingly prevalent in East Asia. Its pathogenesis is linked to microbiota dysbiosis via the oral-gut axis, but population-specific causal evidence remains scarce. This study aimed to clarify the causal associations between oral microbiota and UC/CD in East Asian populations using Mendelian randomization (MR), providing evidence for IBD etiology and precise prevention/treatment. A 2-sample MR approach was adopted, using genome-wide association study data of East Asian populations. Single nucleotide polymorphisms associated with tongue dorsum and salivary microbiota were selected as instrumental variables after rigorous screening (F-statistic > 10, linkage disequilibrium R2 = 0.001). Inverse variance weighted was the primary analysis method, supplemented by sensitivity tests (MR-PRESSO, MR-Egger intercept test, etc) and Benjamini-Hochberg multiple testing correction (false discovery rate < 0.05). A total of 82 oral microbiota taxa (22 families, 35 genera) were significantly causally associated with UC (FDR < 0.05), and 21 taxa (10 families, 12 genera) with CD (FDR < 0.05). High-risk taxa included Aggregatibacter and Streptococcus (OR > 1), while protective taxa included Fusobacterium_periodonticum_C_mgs_3022 and TM7x_unclassified_mgs_1084 (OR < 1). A distinct "mixed effect" was identified: the Streptococcus genus was risky for UC but protective for CD; genera such as Streptococcus (UC), Oribacterium (CD), and TM7x (CD) exhibited bidirectional risk/protective associations within a single IBD subtype; and the TM7x genus was risky for UC and showed bidirectional effects in CD. Other genera (e.g., Fusobacterium, Aggregatibacter) only had unidirectional associations. This study is the first to confirm the causal association between oral microbiota and IBD in East Asian populations, revealing the heterogeneity and "mixed effect" of this association. Identified high-risk and protective oral microbiota taxa provide new insights into IBD etiology and potential targets for clinical precise prevention and treatment.