Haas Melanie, Brandl Beate, Neuhaus Klaus, Wudy Susanne, Kleigrewe Karin, Hauner Hans, Skurk Thomas
Core Facility Human Studies, ZIEL Institute for Food & Health, Technical University of Munich, Freising, Germany.
Core Facility Microbiome, ZIEL Institute for Food & Health, Technical University of Munich, Freising, Germany.
Eur J Clin Nutr. 2025 Jun 19. doi: 10.1038/s41430-025-01636-8.
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.
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.
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 .
背景/目的：肠道微生物群依赖的代谢物氧化三甲胺（TMAO）与心血管疾病（CVD）风险相关，而膳食纤维与降低CVD风险及改善肠道健康有关。考虑到这些关联，我们进行了一项随机、双盲的试点研究，以调查补充膳食纤维对食用牛肉后肠道TMAO形成的影响。
受试者/方法：13名志愿者接受了为期两周的膳食纤维和安慰剂干预。我们评估了补充膳食纤维对肠道微生物群以及cutC酶基因丰度的影响，cutC酶是微生物形成TMA（TMAO的前体）的关键酶。我们在为期两周的干预后测量了食用牛肉后的TMAO反应。我们还研究了肝脏酶FMO3对血浆TMAO水平的作用。
尽管膳食纤维组和安慰剂组之间的总体TMAO生成量没有变化（p值 = 0.26，95%置信区间），但亚组分析显示，在习惯性肉类摄入量较低（每周<3次）的参与者中，补充膳食纤维可减弱食用牛肉后TMAO的形成（p值 = 0.029，95%置信区间）。此外，纤维干预显著下调了微生物cutC基因的丰度（p = 0.034，95%置信区间），这表明纤维可能降低血浆TMAO水平的一种机制。虽然膳食纤维干预在所有参与者中并未改变TMAO的生成，但在习惯性肉类摄入量较低的个体中显示出潜在效果。观察到的cutC基因丰度下调表明了纤维对TMAO形成产生有益影响的一种机制。
这些发现支持高纤维、低肉类饮食作为减轻与TMAO相关的CVD风险的一种有前景策略的作用。MEATMARK研究的图形摘要。由BioRender.com创建。哈斯，M.（2025年）https://BioRender.com/x12v771 。
