Dynamics of intestinal microbial trimethylamine production in Göttingen minipigs

Human gut bacteria metabolize dietary components such as choline, converting it to trimethylamine (TMA), which is subsequently oxidised by hepatic enzymes to yield trimethylamine-N-oxide (TMAO). Increased plasma TMAO levels are reported to exacerbate atherosclerosis in mice and are positively correlated with the severity of atherosclerosis in humans. In order to obtain detailed insights into dynamics of TMA production from choline, we performed a longitudinal short-term dietary intervention study in ileo-cecal fistulated Göttingen minipigs, using a baseline diet (0.36 g choline/kg) and a choline-rich diet (~3.84 g choline/kg). We determined the abundance of the gene cutC encoding the choline TMA lyase by quantitative PCR in both ileal chyme and fecal samples, and sequenced amplified products on Illumina MiSeq. Furthermore, we quantified levels of the urinary metabolites choline, TMA and TMAO using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS).Community structure of microbial cutC community was similar to that of humans and displayed alterations by the influence of dietary choline that were site-specific. During the choline-enriched diet metabolite concentrations in urines were elevated.