Abstract

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.

Highlights

  • Advanced glycation end products (AGEs) are a heterogeneous group of compounds that are formed by the non-enzymatic reaction of reducing α-carbonylic compounds with free amino groups in proteins, lipids and nucleic acids resulting in alteration in their function [1,2,3]

  • 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

  • We aimed to evaluate the effect of restricting a habitually high dietary AGEs (dAGEs) consumption on gut microbiota in a group of end stage renal disease (ESRD) patients on maintenance peritoneal dialysis (PD), and hypothesize that dAGE restriction affects the diversity of bacterial gut microbiota in patients with ESRD receiving maintenance PD

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Summary

Introduction

Advanced glycation end products (AGEs) are a heterogeneous group of compounds that are formed by the non-enzymatic reaction of reducing α-carbonylic compounds with free amino groups in proteins, lipids and nucleic acids resulting in alteration in their function [1,2,3]. AGEs are constantly formed at a small rate endogenously and a significant amount is consumed as food. AGE accumulation can be harmful through several mechanisms including affecting protein structure and function by directly cross-linking with them, or by activating cellular receptors [15,16,17,18]. In patients with end stage renal disease (ESRD) requiring hemodialysis (HD) or peritoneal dialysis (PD), AGEs build up in the body due to impaired urinary elimination and limited clearance during dialysis [19,20,21]

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