Choline Source, Gut Microbiota and Trimethylamine-N-oxide Response

Metabolism Clinical Trial

Official title:

Effect of Choline Source and Gut Microbiota Composition on Trimethylamine-N-oxide Response in Humans

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04255368
• Other study ID #: 8547
• Status: Completed
• Phase: N/A
• Start date: November 9, 2017
• Est. completion date: July 25, 2020

Study information

• Verified date: November 2020
• Source: Utah State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 44
• Est. completion date: July 25, 2020
• Est. primary completion date: June 16, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Metabolism

Intervention

Other:
• Water-soluble choline
600 mg choline as choline bitartrate
• Fat-soluble choline
600 mg choline as phosphatidylcholine
• No choline control
No choline

Locations

Country	Name	City	State
United States	Center for Human Nutrition Studies Clinic, Utah State University	Logan	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Utah State University

Country where clinical trial is conducted

United States, 

References & Publications (3)

Cho CE, Taesuwan S, Malysheva OV, Bender E, Tulchinsky NF, Yan J, Sutter JL, Caudill MA. Trimethylamine-N-oxide (TMAO) response to animal source foods varies among healthy young men and is influenced by their gut microbiota composition: A randomized controlled trial. Mol Nutr Food Res. 2017 Jan;61(1). doi: 10.1002/mnfr.201600324. Epub 2016 Aug 3. — View Citation

Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013 Apr 25;368(17):1575-84. doi: 10.1056/NEJMoa1109400. — View Citation

Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011 Apr 7;472(7341):57-63. doi: 10.1038/nature09922. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	TMAO metabolite concentration change	Plasma TMAO metabolite response	Blood: study baseline, 30 minutes and 1 hour, 2 hours, 4 hours and 6 hours
Primary	TMAO metabolite concentration change	Urinary TMAO metabolite response	Urine: study baseline, pooled 6 hours study period
Primary	Gut microbiome profile	16S rRNA	Stool: one-time baseline
Secondary	One-carbon metabolite concentration change	Plasma choline metabolite response	Blood: study baseline, 30 minutes and 1 hour, 2 hours, 4 hours and 6 hours
Secondary	Phosphatidylcholine concentration change	Plasma phosphatidylcholine response	Blood: study baseline, 30 minutes and 1 hour, 2 hours, 4 hours and 6 hours
Secondary	One-carbon metabolite concentration change	Urinary choline metabolite response	Urine: study baseline, pooled 6 hours study period
Secondary	Inflammation and cardiovascular disease risk marker concentration change	Plasma TNF-a and IL-6	Blood: study baseline to 6 hours
Secondary	Flavin monooxygenase 3 (FMO3) 472 G>A genotype variant	Genetic polymorphism	Blood: study baseline