Advanced glycation end products dietary restriction effects on bacterial gut microbiota in peritoneal dialysis patients; a randomized open label controlled trial

The modern Western diet is rich in advanced glycation end products (AGEs). We have previously shown an association between dietary AGEs and markers of inflammation and oxidative stress in a population of end stage renal disease (ESRD) patients undergoing peritoneal dialysis (PD). In the current pilot study we explored the effects of dietary AGEs on the gut bacterial microbiota composition in similar patients. AGEs play an important role in the development and progression of cardiovascular (CVD) disease. Plasma concentrations of different bacterial products have been shown to predict the risk of incident major adverse CVD events independently of traditional CVD risk factors, and experimental animal models indicates a possible role AGEs might have on the gut microbiota population. In this pilot randomized open label controlled trial, twenty PD patients habitually consuming a high AGE diet were recruited and randomized into either continuing the same diet (HAGE, n = 10) or a one-month dietary AGE restriction (LAGE, n = 10). Blood and stool samples were collected at baseline and after intervention. Variable regions V3-V4 of 16s rDNA were sequenced and taxa was identified on the phyla, genus, and species levels. Dietary AGE restriction resulted in a significant decrease in serum Nε-(carboxymethyl) lysine (CML) and methylglyoxal-derivatives (MG). At baseline, our total cohort exhibited a lower relative abundance of Bacteroides and Alistipes genus and a higher abundance of Prevotella genus when compared to the published data of healthy population. Dietary AGE restriction altered the bacterial gut microbiota with a significant reduction in Prevotella copri and Bifidobacterium animalis relative abundance and increased Alistipes indistinctus, Clostridium citroniae, Clostridium hathewayi, and Ruminococcus gauvreauii relative abundance. We show in this pilot study significant microbiota differences in peritoneal dialysis patients’ population, as well as the effects of dietary AGEs on gut microbiota, which might play a role in the increased cardiovascular events in this population and warrants further studies.

现代西式饮食富含晚期糖基化终末产物（advanced glycation end products, AGEs）。我们既往曾在接受腹膜透析（peritoneal dialysis, PD）的终末期肾病（end stage renal disease, ESRD）患者群体中，证实膳食AGEs与炎症及氧化应激标志物之间存在关联。本项先导性研究旨在探究膳食AGEs对同类患者肠道细菌菌群组成的影响。AGEs在心血管（cardiovascular, CVD）疾病的发生与进展中发挥关键作用。已有研究表明，不同细菌产物的血浆浓度可独立于传统CVD危险因素，预测主要不良心血管事件的发生风险；同时动物实验模型提示，AGEs或许对肠道菌群种群具有调控作用。本项随机开放标签对照先导试验共招募20名习惯性摄入高AGE饮食的PD患者，将其随机分为两组：继续原有高AGE饮食组（HAGE，n=10），以及实施为期1个月膳食AGE限制的干预组（LAGE，n=10）。分别于基线状态及干预结束后采集血液与粪便样本。对16S核糖体DNA（16s rDNA）的V3-V4可变区进行测序，并在门、属及物种水平上对菌群分类单元进行鉴定。膳食AGE限制干预可显著降低血清Nε-（羧甲基）赖氨酸（Nε-(carboxymethyl) lysine, CML）与甲基乙二醛衍生物（methylglyoxal-derivatives, MG）水平。基线状态下，相较于已发表的健康人群数据，本研究全部受试者队列表现为拟杆菌属（Bacteroides）与别样杆菌属（Alistipes）相对丰度偏低，而普雷沃氏菌属（Prevotella）相对丰度偏高。膳食AGE限制干预可改变肠道细菌菌群组成：普雷沃氏菌copri（Prevotella copri）与动物双歧杆菌（Bifidobacterium animalis）的相对丰度显著降低，而别样杆菌未定种（Alistipes indistinctus）、柠檬梭菌（Clostridium citroniae）、哈氏梭菌（Clostridium hathewayi）及高氏瘤胃球菌（Ruminococcus gauvreauii）的相对丰度显著升高。本先导性研究证实，腹膜透析患者群体的肠道菌群存在显著差异，同时揭示了膳食AGEs对肠道菌群的调控作用——这一作用或与该群体心血管事件发生率升高相关，有待开展进一步研究。