Choline Source, Gut Microbiota and Trimethylamine-N-oxide Response
- Conditions
- Metabolism
- Interventions
- Other: Water-soluble cholineOther: No choline controlOther: Fat-soluble choline
- Registration Number
- NCT04255368
- Lead Sponsor
- Utah State University
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 44
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Water-soluble choline Water-soluble choline A breakfast meal consisting of 1 cup of tomato soup containing 600 mg choline as choline bitartrate; served with a bagel with margarine-butter spread and one cup of water. No choline No choline control A breakfast meal consisting of 1 cup of tomato soup containing no choline; served with a bagel with margarine-butter spread and one cup of water. Fat-soluble choline Fat-soluble choline A breakfast meal consisting of 1 cup of tomato soup containing 600 mg choline as phosphatidylcholine; served with a bagel with margarine-butter spread and one cup of water.
- Primary Outcome Measures
Name Time Method TMAO metabolite concentration change Urine: study baseline, pooled 6 hours study period Urinary TMAO metabolite response
Gut microbiome profile Stool: one-time baseline 16S rRNA
- Secondary Outcome Measures
Name Time Method 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
One-carbon metabolite concentration change Urine: study baseline, pooled 6 hours study period Urinary choline metabolite response
Flavin monooxygenase 3 (FMO3) 472 G>A genotype variant Blood: study baseline Genetic polymorphism
Trial Locations
- Locations (1)
Center for Human Nutrition Studies Clinic, Utah State University
🇺🇸Logan, Utah, United States