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

• Published in: Nutrients Vol. 12; no. 8; p. 2220
• Main Authors: Cho, Clara E., Aardema, Niklas D. J., Bunnell, Madison L., Larson, Deanna P., Aguilar, Sheryl S., Bergeson, Janet R., Malysheva, Olga V., Caudill, Marie A., Lefevre, Michael
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25.07.2020; MDPI
• Subjects: Adult; Biomarkers - blood; Biomarkers - urine; Blood; cardiovascular diseases; Cardiovascular Diseases - etiology; choline; Choline - administration & dosage; Clostridium; Cross-Over Studies; Diet - adverse effects; Dietary Supplements; digestive system; Double-Blind Method; Female; Gastrointestinal Microbiome - drug effects; Gut microbiota; Healthy Volunteers; Heart Disease Risk Factors; Humans; intestinal microorganisms; Lachnospiraceae; Male; Meals; Meals - physiology; metabolites; Methylamines - blood; Methylamines - urine; microbiome; Microbiota; Middle Aged; multivariate analysis; Nutrition; phosphatidylcholines; Phosphatidylcholines - administration & dosage; risk factors; Ruminococcaceae; Urine; Womens health; United States > US; Utah; trimethylamine-N-oxide; choline; metabolism; dietary precursor intake; gut microbiota
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu12082220

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