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Trimethylamine N-oxide and risk of inflammatory bowel disease: A Mendelian randomization study
Yukika Banno1, Miho Nomura, Risako Hara
1School of Nutrition and Dietetics, Faculty of Health and Social Services, Kanagawa University of Human Services, Yokosuka, Kanagawa, Japan.
Abstract:
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.
Insights
This study investigated the link between trimethylamine N-oxide (TMAO) and inflammatory bowel disease (IBD). Mendelian randomization analysis found no significant causal relationship between genetically predicted TMAO levels and IBD risk.
Area of Science:
- Gastroenterology and Metabolism
Background:
- Previous research suggested a potential link between low plasma trimethylamine N-oxide (TMAO) levels and inflammatory bowel disease (IBD).
- This study aimed to rigorously investigate the causal relationship between TMAO and IBD using a robust genetic approach.
Approach:
- Employed Mendelian randomization analysis utilizing summary statistics from genome-wide association studies.
- Analyzed single-nucleotide polymorphisms associated with plasma TMAO levels and IBD in a large cohort (59,957 individuals).
- Assessed potential pleiotropy using Mendelian randomization-Egger regression to ensure analytical validity.
Key Points:
- Genetically predicted higher plasma TMAO levels showed a non-significant inverse association with IBD risk (OR 0.91, 95% CI 0.81-1.01, P=0.084).
- Similar non-significant trends were observed for ulcerative colitis and Crohn disease.
- Mendelian randomization-Egger regression indicated no significant evidence of pleiotropy, supporting the validity of the primary analysis.
Conclusions:
- The current Mendelian randomization analysis does not support a causal link between genetically determined plasma TMAO levels and the risk of developing IBD.
- Further research is warranted to fully elucidate the complex interplay between TMAO metabolism and gastrointestinal health.
