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

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

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.

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