Interplay between the (Poly)phenol Metabolome, Gut Microbiome, and Cardiovascular Health in Women: A Cross-Sectional Study from the TwinsUK Cohort.
Interplay between the (Poly)phenol Metabolome, Gut Microbiome, and Cardiovascular Health in Women: A Cross-Sectional Study from the TwinsUK Cohort.
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DOI：
10.3390/nu15081900
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发表时间：
2023-04-14
期刊：
影响因子：
5.9
通讯作者：
Rodriguez-Mateos A
中科院分区：
文献类型：
--
作者：
Li Y;Xu Y;Le Roy C;Hu J;Steves CJ;Bell JT;Spector TD;Gibson R;Menni C;Rodriguez-Mateos A
工作背景：在流行病学研究中，膳食（多酚）摄入量与心血管疾病（CVD）风险呈负相关，但对肠道微生物组在这种关系中的作用知之甚少。研究方法：在来自TwinsUK队列的200名年龄为62.0 ± 10.0岁的健康女性中，使用超高效液相色谱-质谱法从点尿中测定了114种单个（多）酚代谢物。使用调整年龄、BMI、纤维、能量摄入、家庭相关性和多重检验（FDR <0.1）的线性混合模型研究代谢物、肠道微生物组（α多样性和属）和心血管评分之间的关联。结果：酚酸代谢物、CVD风险和肠道微生物组之间存在显著相关性。共有35种酚酸代谢物与厚壁菌门相关，而5种代谢物与α多样性相关（FDR调整的p <0.05）。动脉粥样硬化性心血管疾病（ASCVD）风险评分与5种酚酸代谢物、2种酪醇代谢物和大豆苷元之间存在负相关性，标准β（95%（CI））范围为3-（2，4-二羟基苯基）丙酸的− 0.05（− 0.09，− 0.01）至2-羟基肉桂酸的− 0.04（− 0.08，− 0.003）（FDR校正p <0.1）。拟杆菌门中的5 - 7N15属与相同的代谢物正相关，包括3-（3，5-二羟基苯基）丙酸，3-（2，4-二羟基苯基）丙酸，3-（3，4-二羟基苯基）丙酸）、3-羟基苯基乙醇-4-硫酸盐和4-羟基苯基乙醇-3-硫酸盐）（stdBeta（95%CI）：0.23（0.09，0.36）至0.28（0.15，0.42），FDR调整的p <0.05），与ASCVD评分呈负相关（stdBeta（95%CI）：-0.05（-0.09，-0.01），FDR调整的p = 0.02）。介导分析显示，属5 - 7N15介导了3-（3，4-二羟基苯基）丙酸对ASCVD评分的总效应的23.8%。结论：咖啡、茶、红酒和几种蔬菜和水果，尤其是浆果，是酚酸最丰富的食物来源，与CVD风险有最强的关联。我们发现，肠道微生物组，特别是5 - 7N15属，部分介导了尿（多）酚与心血管风险之间的负相关性，支持肠道微生物组在膳食（多）酚的健康益处中的关键作用。
Background: Dietary (poly)phenol consumption is inversely associated with cardiovascular disease (CVD) risk in epidemiological studies, but little is known about the role of the gut microbiome in this relationship. Methods: In 200 healthy females, aged 62.0 ± 10.0 years, from the TwinsUK cohort, 114 individual (poly)phenol metabolites were measured from spot urine using ultra-high-performance liquid chromatography–mass spectrometry. The associations between metabolites, the gut microbiome (alpha diversity and genera), and cardiovascular scores were investigated using linear mixed models adjusting age, BMI, fibre, energy intake, family relatedness, and multiple testing (FDR < 0.1). Results: Significant associations were found between phenolic acid metabolites, CVD risk, and the gut microbiome. A total of 35 phenolic acid metabolites were associated with the Firmicutes phylum, while 5 metabolites were associated with alpha diversity (FDR-adjusted p < 0.05). Negative associations were observed between the atherosclerotic CVD (ASCVD) risk score and five phenolic acid metabolites, two tyrosol metabolites, and daidzein with stdBeta (95% (CI)) ranging from −0.05 (−0.09, −0.01) for 3-(2,4-dihydroxyphenyl)propanoic acid to −0.04 (−0.08, −0.003) for 2-hydroxycinnamic acid (FDR-adjusted p < 0.1). The genus 5-7N15 in the Bacteroidetes phylum was positively associated with the same metabolites, including 3-(3,5-dihydroxyphenyl)propanoic acid, 3-(2,4-dihydroxyphenyl)propanoic acid, 3-(3,4-dihydroxyphenyl)propanoic acid), 3-hydroxyphenylethanol-4-sulfate, and 4-hydroxyphenylethanol-3-sulfate)(stdBeta (95% CI): 0.23 (0.09, 0.36) to 0.28 (0.15, 0.42), FDR-adjusted p < 0.05), and negatively associated with the ASCVD score (stdBeta (95% CI): −0.05 (−0.09, −0.01), FDR-adjusted p = 0.02). Mediation analysis showed that genus 5-7N15 mediated 23.8% of the total effect of 3-(3,4-dihydroxyphenyl)propanoic acid on the ASCVD score. Conclusions: Coffee, tea, red wine, and several vegetables and fruits, especially berries, are the most abundant food sources of phenolic acids that have the strongest associations with CVD risk. We found that the gut microbiome, particularly the genus 5-7N15, partially mediates the negative association between urinary (poly)phenols and cardiovascular risk, supporting a key role of the gut microbiome in the health benefits of dietary (poly)phenols.
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