Effect of dietary fiber on trimethylamine-N-oxide production after beef consumption and on gut microbiota: MEATMARK - a randomized cross-over study.

BACKGROUND/OBJECTIVES: The gut-microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) has been linked to cardiovascular disease (CVD) risk, while dietary fiber is associated with reduced CVD risk and improved gut health. Considering these associations, we conducted a randomized, double-blind, pilot study to investigate the influence of fiber supplementation on intestinal TMAO formation after beef consumption.

SUBJECTS/METHODS: 13 volunteers underwent a two-week dietary fiber and placebo intervention. We assessed the effect of fiber supplementation on the gut microbiota and gene abundance 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 also examined the role of hepatic enzyme FMO3 on TMAO plasma levels.

RESULTS

Although overall TMAO production did not change between the dietary fiber and placebo group (p-value = 0.26, 95% CI), subgroup analysis revealed that fiber supplementation attenuated TMAO formation following beef intake in participants with lower habitual meat consumption ( <3 times/week, p-value = 0.029, 95% CI). Furthermore, fiber intervention significantly downregulated microbial cutC gene abundance (p = 0.034, 95% CI), suggesting a mechanism by which fiber might reduce plasma TMAO levels. While dietary fiber intervention did not alter TMAO production across all participants, it showed a potential effect in individuals with lower habitual meat intake. The observed downregulation of cutC gene abundance suggests a mechanism for the beneficial impact of fiber on TMAO formation.

CONCLUSION

These findings support the role of a high-fiber, low-meat diet as a promising strategy to mitigate TMAO-related CVD risk. Graphical abstract of the MEATMARK study. Created with BioRender.com. Haas, M. (2025) https://BioRender.com/x12v771 .