Trimethylamine N-oxide and risk of inflammatory bowel disease: A Mendelian randomization study

A previous study suggested that inflammatory bowel disease (IBD) patients have low plasma levels of trimethylamine N-oxide (TMAO). In the present study, we examined this hypothesis using Mendelian randomization analysis. We used summary statistics data for single-nucleotide polymorphisms associated with plasma levels of TMAO, and the corresponding data for IBD from a genome-wide association meta-analysis of 59,957 individuals (25,042 diagnosed IBD cases, 34,915 controls). The association between genetically predicted plasma TMAO levels and IBD showed odds ratios (95% confidence interval [CI]) per 1 interquartile range increment (per 2.4 μmol/L) in TMAO levels were 0.91 (0.81–1.01, P = .084) for IBD, 0.88 (0.76–1.02, P = .089) for ulcerative colitis, 0.91 (0.79–1.05, P = .210) for Crohn disease. There was no evidence for pleiotropy based on the Mendelian randomization-Egger regression analyses (P-intercept = 0.669 for IBD). Further investigations would be needed to understand the causal relationship between TMAO and IBD.