多酚丰富饮食对“肠漏”老年人肠道屏障、肠道微生物群和血清代谢组学的交叉对话：MaPLE 试验。

Crosstalk among intestinal barrier, gut microbiota and serum metabolome after a polyphenol-rich diet in older subjects with "leaky gut": The MaPLE trial.

机构信息

Biomarkers and Nutrimetabolomics Laboratory, Department of Nutrition, Food Sciences and Gastronomy, Food Innovation Network (XIA), Nutrition and Food Safety Research Institute (INSA), Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028, Barcelona, Spain; Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Spain.

Department of Food, Environmental and Nutritional Sciences (DeFENS), Università Degli Studi di Milano, 20133, Milan, Italy.

出版信息

Clin Nutr. 2021 Oct;40(10):5288-5297. doi: 10.1016/j.clnu.2021.08.027. Epub 2021 Sep 9.

DOI:10.1016/j.clnu.2021.08.027

PMID:34534897

Abstract

BACKGROUND &AIM: The MaPLE study was a randomized, controlled, crossover trial involving adults ≥60 y.o. (n = 51) living in a residential care facility during an 8-week polyphenol-rich (PR)-diet. Results from the MaPLE trial showed that the PR-diet reduced the intestinal permeability (IP) in older adults by inducing changes to gut microbiota (GM). The present work aimed at studying the changes in serum metabolome in the MaPLE trial, as a further necessary step to depict the complex crosstalk between dietary polyphenols, GM, and intestinal barrier.

METHODS

Serum metabolome was monitored using a semi-targeted UHPLC-MS/MS analysis. Metataxonomic analysis (16S rRNA gene profiling) of GM was performed on faecal samples. Clinical characteristics and serum levels of the IP marker zonulin were linked to GM and metabolomics data in a multi-omics network.

RESULTS

Compared to the control diet, the PR-diet increased serum metabolites related to polyphenols and methylxanthine intake. Theobromine and methylxanthines, derived from cocoa and/or green tea, were positively correlated with butyrate-producing bacteria (the order Clostridiales and the genera Roseburia, Butyricicoccus and Faecalibacterium) and inversely with zonulin. A direct correlation between polyphenol metabolites hydroxyphenylpropionic acid-sulfate, 2-methylpyrogallol-sulfate and catechol-sulfate with Butyricicoccus was also observed, while hydroxyphenylpropionic acid-sulfate and 2-methylpyrogallol-sulfate negatively correlated with Methanobrevibacter. The multi-omics network indicated that participant's age, baseline zonulin levels, and changes in Porphyromonadaceae abundance were the main factors driving the effects of a PR-diet on zonulin.

CONCLUSION

Overall, these results reveal the complex relationships among polyphenols consumption, intestinal permeability, and GM composition in older adults, and they may be important when setting personalized dietary interventions for older adults.

TRIAL REGISTRATION NUMBER

ISRCTN10214981.

摘要

背景与目的

MaPLE 研究是一项涉及居住在养老院的 60 岁及以上成年人（n=51）的随机、对照、交叉试验，试验为期 8 周，参与者摄入富含多酚的饮食。MaPLE 研究结果表明，富含多酚的饮食通过改变肠道微生物群（GM）来降低老年人的肠道通透性（IP）。本研究旨在研究 MaPLE 试验中血清代谢组的变化，这是描绘膳食多酚、GM 和肠道屏障之间复杂相互作用的必要步骤。

方法

使用半靶向 UHPLC-MS/MS 分析监测血清代谢组。对粪便样本进行 GM 的代谢组学分析（16S rRNA 基因谱分析）。将 GM 和代谢组学数据与临床特征和 IP 标志物肠通透素的血清水平联系起来，构建多组学网络。

结果

与对照饮食相比，富含多酚的饮食增加了与多酚和甲基黄嘌呤摄入相关的血清代谢物。可可和/或绿茶来源的可可因和甲基黄嘌呤与产生丁酸盐的细菌（梭菌目和罗斯伯里氏菌属、丁酸球菌属和粪杆菌属）呈正相关，与肠通透素呈负相关。多酚代谢物对羟基苯丙酸硫酸盐、2-甲基邻苯三酚硫酸盐和儿茶酚硫酸盐与丁酸球菌属也呈直接相关，而对羟基苯丙酸硫酸盐和 2-甲基邻苯三酚硫酸盐与甲烷短杆菌属呈负相关。多组学网络表明，参与者的年龄、基线肠通透素水平和卟啉单胞菌属丰度的变化是富含多酚的饮食对肠通透素产生影响的主要因素。