The purpose of this research is to determine the production of trimethylamine-N-oxide (TMAO) from different forms of choline and whether this response is modified by the gut microbiota composition.
The overall goal of this research is to identify dietary and physiological factors contributing to elevated levels of trimethylamine-N-oxide (TMAO), a choline-derived gut-microbiome-dependent metabolite that has been identified to increase cardiovascular disease risk. Our recent findings indicate that the gut microbiome may account for variations in TMAO levels, whereby those with a greater enrichment of Firmicutes to Bacteroidetes had elevated TMAO response to dietary precursor intake. However, the interaction between choline intake and gut microbiota composition as a determinant of interindividual variations in TMAO response has not been investigated. This study sought to i) compare plasma and urinary TMAO response after acute challenge containing different forms of choline; and ii) to determine the association between differences in TMAO response with differences in gut microbiota composition. To accomplish these objectives, a randomized, controlled cross-over study was conducted in healthy participants (n=41). The study incorporated three arms comprised of study meals containing (i) 600 mg choline as choline bitartrate; (ii) 600 mg choline as phosphatidylcholine; or (iii) no choline. Each meal was served with a bagel with margarine-butter spread and one cup of water, administered in a single day and separated by a 1-week washout period. Baseline blood sample was obtained by a phlebotomist using a standard venipuncture procedure, and participants collected their baseline urine sample. They also turned in a one-time self-collected baseline stool sample. Following the consumption of the study meal, serial blood samples were collected at 30 min and 1, 2, 4 and 6 h, and urine samples collected throughout the 6 h study period. At 4.5 h, participants were provided a fixed fruit snack (i.e., 2 single serving prepackaged applesauce) and water.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
44
600 mg choline as choline bitartrate
600 mg choline as phosphatidylcholine
No choline
Center for Human Nutrition Studies Clinic, Utah State University
Logan, Utah, United States
TMAO metabolite concentration change
Plasma TMAO metabolite response
Time frame: Blood: study baseline, 30 minutes and 1 hour, 2 hours, 4 hours and 6 hours
TMAO metabolite concentration change
Urinary TMAO metabolite response
Time frame: Urine: study baseline, pooled 6 hours study period
Gut microbiome profile
16S rRNA
Time frame: Stool: one-time baseline
One-carbon metabolite concentration change
Plasma choline metabolite response
Time frame: Blood: study baseline, 30 minutes and 1 hour, 2 hours, 4 hours and 6 hours
Phosphatidylcholine concentration change
Plasma phosphatidylcholine response
Time frame: Blood: study baseline, 30 minutes and 1 hour, 2 hours, 4 hours and 6 hours
One-carbon metabolite concentration change
Urinary choline metabolite response
Time frame: Urine: study baseline, pooled 6 hours study period
Inflammation and cardiovascular disease risk marker concentration change
Plasma TNF-α and IL-6
Time frame: Blood: study baseline to 6 hours
Flavin monooxygenase 3 (FMO3) 472 G>A genotype variant
Genetic polymorphism
Time frame: Blood: study baseline
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