Trimethylamine-N-oxide: A Novel Biomarker for the Identification of Inflammatory Bowel Disease

Abstract

Introduction: The gastrointestinal (GI) microbiome is recognized for potential clinical relevance in inflammatory bowel disease (IBD). Data suggest there is a disease-dependent loss of microbial diversity in IBD. Trimethylamine-N-oxide (TMAO) is generated by GI anaerobes through the digestion of dietary phosphatidylcholine and carnitine in a microbial-mammalian co-metabolic pathway. Elevated levels have been linked to heart disease, yet little is known regarding TMAO in IBD. Aim: To determine if TMAO plasma levels in IBD are altered compared to controls and if they correlate with disease presence or activity. Methods: Liquid chromatography-tandem mass spectrometry was used to measure TMAO, choline and carnitine plasma levels in 479 subjects (373 non-IBD controls, 106 IBD). Subjects were also genotyped for the flavin monooxygenase (FMO) 3 variants E158K and E308G. Results: Plasma TMAO levels were 2.27μM lower in the IBD population compared to the control population (p= 0.0001). Lower TMAO levels were similarly seen in active ulcerative colitis (UC) (1.56μM) versus inactive disease (3.40μM) (p= 0.002). No difference was seen in active Crohn's disease (CD) versus inactive CD. No inter-group variation existed in plasma TMAO levels based on FMO3 genotype. Choline levels were higher in IBD, while carnitine levels were similar between the two groups suggesting lower TMAO levels in IBD were not due to dietary differences. Conclusion: Decreased TMAO levels are seen in IBD compared to a non-IBD population. These data suggest that TMAO may have potential as a biomarker to support IBD diagnosis as well as to assess disease activity in UC.