title: Trimethylamine-N-oxide: A Novel Biomarker for the Identification of Inflammatory Bowel Disease.
abstract: BACKGROUND
  The gastrointestinal (GI) microbiome is recognized for potential clinical relevance in inflammatory bowel disease (IBD). Data suggest that 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. IBD-related changes in the gut microbiome may result in disease-specific changes in TMAO plasma concentrations.
  
  
  OBJECTIVE
  To determine whether TMAO plasma levels in IBD are altered compared to controls and whether 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 2.27 µM lower in the IBD population compared to the control population (p = 0.0001). Lower TMAO levels were similarly seen in active ulcerative colitis (UC) (1.56 µM) versus inactive disease (3.40 µM) (p = 0.002). No difference was seen in active Crohn's disease (CD) versus inactive CD. No intergroup 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 that lower TMAO levels in IBD were not due to dietary differences.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Western University, 339 Windermere Road B9-130, London, ON, N6A 5A5, Canada.|Division of Gastroenterology, Department of Medicine, Western University, 339 Windermere Road, London, ON, N6A 5A5, Canada.|Department of Physiology and Pharmacology, Western University, Medical Sciences Building, Rm 216, London, ON, N6A 5C1, Canada.
authors.forename: Aze
authors.initials: A
authors.lastname: Wilson
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Western University, 339 Windermere Road B9-130, London, ON, N6A 5A5, Canada.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Teft
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Western University, 339 Windermere Road B9-130, London, ON, N6A 5A5, Canada.
authors.forename: Bridget L
authors.initials: BL
authors.lastname: Morse
authors.affiliation: Department of Epidemiology and Biostatistics, Western University, Kresge Building, Rm K201, London, ON, N6A 5C1, Canada.
authors.forename: Yun-Hee
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Department of Physiology and Pharmacology, Western University, Medical Sciences Building, Rm 216, London, ON, N6A 5C1, Canada.
authors.forename: Sarah
authors.initials: S
authors.lastname: Woolsey
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Western University, 339 Windermere Road B9-130, London, ON, N6A 5A5, Canada.
authors.forename: Marianne K
authors.initials: MK
authors.lastname: DeGorter
authors.affiliation: Division of Endocrinology, Department of Medicine, Western University, 339 Windermere Road, London, ON, N6A 5A5, Canada.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Hegele
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Western University, 339 Windermere Road B9-130, London, ON, N6A 5A5, Canada.|Department of Physiology and Pharmacology, Western University, Medical Sciences Building, Rm 216, London, ON, N6A 5C1, Canada.
authors.forename: Rommel G
authors.initials: RG
authors.lastname: Tirona
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, Western University, 339 Windermere Road B9-130, London, ON, N6A 5A5, Canada. Richard.Kim@lhsc.on.ca.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Kim
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000097:blood* / Q000175:diagnosis*; D008297:Male; D008744:Methylamines / Q000097:blood*; D008875:Middle Aged; D055815:Young Adult
chemical_list: D015415:Biomarkers; D008744:Methylamines; C005855:trimethyloxamine
keywords: Biomarker; Inflammatory bowel disease; Microbial-mammalian co-metabolism; Trimethylamine-N-oxide