石榴或胡桃鞣花单宁的肠道微生物代谢产物产生两种与心血管代谢风险生物标志物相关的尿石素代谢物类型：在正常体重、超重肥胖和代谢综合征之间的比较。

The gut microbiota metabolism of pomegranate or walnut ellagitannins yields two urolithin-metabotypes that correlate with cardiometabolic risk biomarkers: Comparison between normoweight, overweight-obesity and metabolic syndrome.

机构信息

Research Group on Quality, Safety and Bioactivity of Plant Foods, CEBAS-CSIC, 30100, Campus de Espinardo, Murcia, Spain.

出版信息

Clin Nutr. 2018 Jun;37(3):897-905. doi: 10.1016/j.clnu.2017.03.012. Epub 2017 Mar 16.

DOI:10.1016/j.clnu.2017.03.012

PMID:28347564

Abstract

BACKGROUND & AIMS: Urolithins are microbial metabolites produced after consumption of ellagitannin-containing foods such as pomegranates and walnuts. Parallel to isoflavone-metabolizing phenotypes, ellagitannin-metabolizing phenotypes (urolithin metabotypes A, B and 0; UM-A, UM-B and UM-0, respectively) can vary among individuals depending on their body mass index (BMI), but correlations between urolithin metabotypes (UMs) and cardiometabolic risk (CMR) factors are unexplored. We investigated the association between UMs and CMR factors in individuals with different BMI and health status.

METHODS

UM was identified using UPLC-ESI-qToF-MS in individuals consuming pomegranate or nuts. The associations between basal CMR factors and the urine urolithin metabolomic signature were explored in 20 healthy normoweight individuals consuming walnuts (30 g/d), 49 healthy overweight-obese individuals ingesting pomegranate extract (450 mg/d) and 25 metabolic syndrome (MetS) patients consuming nuts (15 g-walnuts, 7.5 g-hazelnuts and 7.5 g-almonds/d).

RESULTS

Correlations between CMR factors and urolithins were found in overweight-obese individuals. Urolithin-A (mostly present in UM-A) was positively correlated with apolipoprotein A-I (P ≤ 0.05) and intermediate-HDL-cholesterol (P ≤ 0.05) while urolithin-B and isourolithin-A (characteristic from UM-B) were positively correlated with total-cholesterol, LDL-cholesterol (P ≤ 0.001), apolipoprotein B (P ≤ 0.01), VLDL-cholesterol, IDL-cholesterol, oxidized-LDL and apolipoprotein B:apolipoprotein A-I ratio (P ≤ 0.05). In MetS patients, urolithin-A only correlated inversely with glucose (P ≤ 0.05). Statin-treated MetS patients with UM-A showed a lipid profile similar to that of healthy normoweight individuals while a poor response to lipid-lowering therapy was observed in MB patients.

CONCLUSIONS

UMs are potential CMR biomarkers. Overweight-obese individuals with UM-B are at increased risk of cardiometabolic disease, whereas urolithin-A production could protect against CMR factors. Further research is warranted to explore these associations in larger cohorts and whether the effect of lipid-lowering drugs or ellagitannin-consumption on CMR biomarkers depends on individuals' UM.

CLINICAL TRIAL REGISTRY NUMBERS AND WEBSITES

NCT01916239 (https://clinicaltrials.gov/ct2/show/NCT01916239) and ISRCTN36468613 (http://www.isrctn.com/ISRCTN36468613).

摘要

背景与目的

鞣花单宁是石榴和核桃等含有鞣花单宁的食物被人体摄入后产生的微生物代谢产物。类似于大豆异黄酮代谢表型，鞣花单宁代谢表型（尿石素代谢型 A、B 和 0；UM-A、UM-B 和 UM-0）在个体之间存在差异，这取决于他们的体重指数（BMI），但尿石素代谢型（UM）与心脏代谢风险（CMR）因素之间的相关性尚未得到探索。我们研究了不同 BMI 和健康状况的个体中 UMs 与 CMR 因素之间的关系。

方法

使用 UPLC-ESI-qToF-MS 在食用石榴或坚果的个体中鉴定 UM。在 20 名健康正常体重个体食用核桃（30g/d）、49 名健康超重肥胖个体摄入石榴提取物（450mg/d）和 25 名代谢综合征（MetS）患者食用坚果（15g-核桃、7.5g-榛子和 7.5g-杏仁/d）的情况下，探讨了基础 CMR 因素与尿液尿石素代谢组学特征之间的关系。

结果

超重肥胖个体中发现 CMR 因素与尿石素之间存在相关性。尿石素 A（主要存在于 UM-A 中）与载脂蛋白 A-I 呈正相关（P≤0.05）和中间高密度脂蛋白胆固醇（P≤0.05），而尿石素 B 和异尿石素 A（特征存在于 UM-B 中）与总胆固醇、LDL 胆固醇（P≤0.001）、载脂蛋白 B（P≤0.01）、VLDL 胆固醇、IDL 胆固醇、氧化 LDL 和载脂蛋白 B:载脂蛋白 A-I 比值呈正相关（P≤0.05）。在 MetS 患者中，尿石素 A 仅与葡萄糖呈负相关（P≤0.05）。具有 UM-A 的他汀类药物治疗的 MetS 患者表现出与健康正常体重个体相似的血脂谱，而 MB 患者对降脂治疗的反应较差。