Burns Kaelyn F, Blair Rachael Hageman, LaMonte Michael J, Wactawski-Wende Jean, Rexrode Kathryn M, Balasubramanian Raji, Tabung Fred K, Snetselaar Linda, Millen Amy E
Department of Epidemiology and Environmental Health, University at Buffalo, 270 Farber Hall, Buffalo, NY, 14214, USA.
Department of Biostatistics, University at Buffalo, Buffalo, NY, 14214, USA.
Eur J Nutr. 2025 Sep 4;64(6):271. doi: 10.1007/s00394-025-03792-w.
We previously identified a dietary pattern (DP) associated with plasma trimethylamine -oxide (TMAO) and choline, the TMAO-DP, where higher scores represent more atherogenic potential of the diet. The mechanisms linking dietary intake to the presence of choline and TMAO in the plasma, and by which TMAO may influence atherosclerosis in humans require further clarification. The objective was to evaluate associations between the TMAO-DP and metabolomic profiles in postmenopausal women from the Women’s Health Initiative (WHI).
This cross-sectional analysis used baseline WHI data. Dietary intake was assessed using a modified Block food frequency questionnaire. Liquid chromatography-mass spectrometry was used to measure 446 metabolites from plasma samples. Linear regression models were used to evaluate associations between the TMAO-DP and metabolites. Metabolites associated with the TMAO-DP were first identified in a Discovery Sample (WHI Hormone Trials participants; n = 1117) and then were replicated in an independent sample, the Replication Sample (WHI Observational Study participants; n = 870). Pathway enrichment analysis was used to identify overrepresented metabolic pathways in our set of significant metabolites.
There were 132 metabolites associated with the TMAO-DP in the Discovery Sample, and 83 of those were replicated. In the Replication Sample, metabolite classes positively associated with the TMAO-DP included phosphatidylcholine plasmalogen, phosphatidylethanolamine plasmalogen, and acyl carnitine, and the metabolite classes negatively associated included phosphatidylcholine and cholesterol ester. Overrepresented pathways included pathways of lipid metabolism.
This study provides insights into the metabolic processes linking dietary intake to TMAO production, and TMAO to atherosclerosis, among postmenopausal women.
The online version contains supplementary material available at 10.1007/s00394-025-03792-w.
我们之前确定了一种与血浆氧化三甲胺（TMAO）和胆碱相关的饮食模式（DP），即TMAO-DP，得分越高表明饮食的动脉粥样硬化潜力越大。饮食摄入与血浆中胆碱和TMAO存在之间的联系机制，以及TMAO可能影响人类动脉粥样硬化的机制，需要进一步阐明。目的是评估女性健康倡议（WHI）中绝经后女性的TMAO-DP与代谢组学特征之间的关联。
这项横断面分析使用了WHI的基线数据。饮食摄入量通过改良的Block食物频率问卷进行评估。采用液相色谱-质谱法测量血浆样本中的446种代谢物。线性回归模型用于评估TMAO-DP与代谢物之间的关联。与TMAO-DP相关的代谢物首先在发现样本（WHI激素试验参与者；n = 1117）中确定，然后在独立样本即复制样本（WHI观察性研究参与者；n = 870）中进行复制。通路富集分析用于确定我们一组显著代谢物中过度代表的代谢通路。
在发现样本中有132种代谢物与TMAO-DP相关，其中83种得到了复制。在复制样本中，与TMAO-DP呈正相关的代谢物类别包括缩醛磷脂酰胆碱、缩醛磷脂酰乙醇胺和酰基肉碱，呈负相关的代谢物类别包括磷脂酰胆碱和胆固醇酯。过度代表的通路包括脂质代谢通路。
本研究深入探讨了绝经后女性中饮食摄入与TMAO产生以及TMAO与动脉粥样硬化之间的代谢过程。
在线版本包含可在10.1007/s00394-025-03792-w获取的补充材料。
