Dietary fiber intervention modulates the formation of the cardiovascular risk factor trimethylamine-N-oxide after beef consumption

Objective: The gut-microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) has emerged as a potential risk factor for cardiovascular disease (CVD). Conversely, dietary fiber has been associated with a reduced risk of CVD and been proposed to exhibit beneficial effects on gut health. Considering these associations, we conducted an intervention study to investigate the influence of fiber supplementation on intestinal TMAO formation and its response after beef consumption. Approach and Results: Our randomized, double blind, pilot study MEATMARK included thirteen volunteers who underwent a dietary fiber and placebo intervention over two weeks. We assessed the effect of fiber supplementation on the gut microbiota and expression of the enzyme cutC, a key enzyme for microbial TMA formation, a precursor for TMAO. We measured the TMAO response following beef consumption after the two-week intervention. We further investigated the impact of three human single nucleotide polymorphisms (SNPs) in the expression of the hepatic enzyme FMO3 on TMAO plasma levels, as this factor is responsible for the final oxidation step from TMA to TMAO. Conclusion: Our findings indicate that dietary fiber supplementation attenuated TMAO formation after beef intake, particularly in participants with habitual lower daily meat consumption. Furthermore, we observed a significant downregulation of cutC expression in response to the fiber intervention, suggesting a potential mechanism to reduce plasma TMAO. Considering these findings, a high fiber, low meat diet presents a promising dietary strategy for reducing this CVD risk factor.