Effect of Choline Forms and Gut Microbiota Composition on Trimethylamine- N-Oxide Response in Healthy Men

Nutrients. 2020 Jul 25;12(8):2220. doi: 10.3390/nu12082220.

Abstract

Background: Trimethylamine-N-oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, is a newly recognized risk marker for cardiovascular disease. We sought to determine: (1) TMAO response to meals containing free versus lipid-soluble choline and (2) effects of gut microbiome on TMAO response.

Methods: In a randomized, controlled, double-blinded, crossover study, healthy men (n = 37) were provided meals containing 600 mg choline either as choline bitartrate or phosphatidylcholine, or no choline control.

Results: Choline bitartrate yielded three-times greater plasma TMAO AUC (p = 0.01) and 2.5-times greater urinary TMAO change from baseline (p = 0.01) compared to no choline and phosphatidylcholine. Gut microbiota composition differed (permutational multivariate analysis of variance, PERMANOVA; p = 0.01) between high-TMAO producers (with ≥40% increase in urinary TMAO response to choline bitartrate) and low-TMAO producers (with <40% increase in TMAO response). High-TMAO producers had more abundant lineages of Clostridium from Ruminococcaceae and Lachnospiraceae compared to low-TMAO producers (analysis of composition of microbiomes, ANCOM; p < 0.05).

Conclusion: Given that phosphatidylcholine is the major form of choline in food, the absence of TMAO elevation with phosphatidylcholine counters arguments that phosphatidylcholine should be avoided due to TMAO-producing characteristics. Further, development of individualized dietary recommendations based on the gut microbiome may be effective in reducing disease risk.

Keywords: choline; dietary precursor intake; gut microbiota; metabolism; trimethylamine-N-oxide.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Biomarkers / blood
  • Biomarkers / urine
  • Cardiovascular Diseases / etiology
  • Choline / administration & dosage*
  • Cross-Over Studies
  • Diet / adverse effects
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Healthy Volunteers
  • Heart Disease Risk Factors
  • Humans
  • Male
  • Meals / physiology
  • Methylamines / blood*
  • Methylamines / urine*
  • Middle Aged
  • Phosphatidylcholines / administration & dosage

Substances

  • Biomarkers
  • Methylamines
  • Phosphatidylcholines
  • trimethyloxamine
  • Choline