Metabolism
Conditions
Keywords
Dietary precursor, Metabolism, Gut microbiota
Brief summary
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.
Detailed description
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.
Interventions
OTHERWater-soluble choline
600 mg choline as choline bitartrate
OTHERFat-soluble choline
600 mg choline as phosphatidylcholine
OTHERNo choline control
No choline
Sponsors
Utah State University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)
Intervention model description
Randomized, controlled crossover design where participants consume 3 meals containing (i) free choline; (ii) phosphatidylcholine; or (iii) no choline in a random order separated by a 1-week washout period
Eligibility
Sex/Gender
ALL
Age
21 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy men and women of any race or ethnicity * Age 21-50 y * BMI 20-24.9 kg/m2 or BMI 30-39.9 kg/m2
Exclusion criteria
* Age \> 50 y * BMI outside of the normal-weight or obese range (BMI \< 20 kg/m2; BMI 25-29.9 kg/m2; or BMI \> or = 40 kg/m2) * Pregnant or planning to become pregnant during the course of the study; currently breastfeeding (females) * Vegetarians * Smokers or recreational drug users * Individuals with gastrointestinal diseases or complaints, chronic illnesses or other metabolic diseases (including trimethylaminuria) * Individuals who have taken antibiotics within the past 2 months * Individuals who are not willing to discontinue pre- and probiotics and dietary supplements for the time leading up to 2 months before the study and during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| TMAO metabolite concentration change | Blood: study baseline, 30 minutes and 1 hour, 2 hours, 4 hours and 6 hours | Plasma TMAO metabolite response |
| Gut microbiome profile | Stool: one-time baseline | 16S rRNA |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| One-carbon metabolite concentration change | Blood: study baseline, 30 minutes and 1 hour, 2 hours, 4 hours and 6 hours | Plasma choline metabolite response |
| Phosphatidylcholine concentration change | Blood: study baseline, 30 minutes and 1 hour, 2 hours, 4 hours and 6 hours | Plasma phosphatidylcholine response |
| Inflammation and cardiovascular disease risk marker concentration change | Blood: study baseline to 6 hours | Plasma TNF-α and IL-6 |
| Flavin monooxygenase 3 (FMO3) 472 G>A genotype variant | Blood: study baseline | Genetic polymorphism |
Countries
United States
Outcome results
None listed