Effect of Choline Forms and Gut Microbiota Composition on Trimethylamine-N-Oxide Response in Healthy Men

Abstract

Background: Trimethylamine-N-oxide (TMAO), a choline-derived gut microbiota-dependent metabolite, is a newly recognized risk marker for cardiovascular disease. We sought to determine: (1) TMAO response to meals containing free versus lipid-soluble choline and (2) effects of gut microbiome on TMAO response. Methods: In a randomized, controlled, double-blinded, crossover study, healthy men (n = 37) were provided meals containing 600 mg choline either as choline bitartrate or phosphatidylcholine, or no choline control. Results: Choline bitartrate yielded three-times greater plasma TMAO AUC (p = 0.01) and 2.5-times greater urinary TMAO change from baseline (p = 0.01) compared to no choline and phosphatidylcholine. Gut microbiota composition differed (permutational multivariate analysis of variance, PERMANOVA; p = 0.01) between high-TMAO producers (with ≥40% increase in urinary TMAO response to choline bitartrate) and low-TMAO producers (with <40% increase in TMAO response). High-TMAO producers had more abundant lineages of Clostridium from Ruminococcaceae and Lachnospiraceae compared to low-TMAO producers (analysis of composition of microbiomes, ANCOM; p < 0.05). Conclusion: Given that phosphatidylcholine is the major form of choline in food, the absence of TMAO elevation with phosphatidylcholine counters arguments that phosphatidylcholine should be avoided due to TMAO-producing characteristics. Further, development of individualized dietary recommendations based on the gut microbiome may be effective in reducing disease risk

Nutritional Viewpoints on Eggs and Cholesterol

“…However, it is plausible that the phospholipid type of choline may not easily be transformed to TMA in the small intestine than the free forms of choline since PC is relatively smoothly absorbed. This assumption was confirmed by comparing the dietary PC and choline bitartrate, as shown in Figure 5 [140]. This study also emphasized that PC should be avoided due to the large individual difference in TMAO-producing characteristics.…”

“…From these complex situations, the extent of CVD risk that is attributable to TMAO may also differ individually [124,140]. A higher circulating concentration of TMAO may not simply be interpreted as a marker of unhealthy food intake or an unhealthy dietary pattern.…”

Long-Term Effects of Bariatric Surgery on Gut Microbiota Composition and Faecal Metabolome Related to Obesity Remission

“…Finally, Lachnospira decreased significantly in operated patients and was positively correlated with BMI, body fat and insulin levels, unlike a previous study in which Lachnospira was negatively correlated with BMI and fasting blood glucose [ 43 ]. Moreover, this genus correlated positively with TMAO and decreased with bariatric surgery, which is in accordance with its reported ability to produce this metabolite [ 44 ]. Furthermore, a recent study of the alterations on microbiota in childhood obesity showed that Lachnospira was significantly elevated in patients with obesity [ 45 ].…”

“…Although an increased concentration of this metabolite has been reported one year after bariatric surgery [48], our results showed that four years after intervention levels of TMAO were reduced, so this may be considered a long-term beneficial effect of bariatric surgery. Additionally, TMAO positively correlated with the presence of Lactococcus genus, which agrees with its role as a minor producer of this metabolite [44].…”

Choline Content of Term and Preterm Infant Formulae Compared to Expressed Breast Milk—How Do We Justify the Discrepancies?

“…Even more important may be bacterial choline degradation prior to its absorption, leading to trimethylamine (TMA) formation, which is subsequently metabolized to TMA oxide (TMAO) by flavin-containing monooxygenase 3 (FMO3; EC 1.14.13.148) in the liver [ 39 ]. In healthy adults, TMAO is not formed from ingested PC, but from free choline provided as choline bitartrate [ 40 ]. Hence, the type of choline supplement may define bioavailability.…”