Abstract

ABSTRACTIntroduction:Gut microbiota imbalance is linked to high uremic toxins production such as indole-3-acetic acid (IAA) in chronic kidney disease patients. This toxin can activate the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor involved with inflammation. Strategies to restore gut microbiota balance can be associated with reduced production of IAA and its deleterious effects. This study aimed to evaluate prebiotic resistant starch (RS) supplementation effects on IAA plasma levels and AhR mRNA expression in CKD patients on hemodialysis (HD).Methods:This randomized, double-blind and placebo-controlled clinical trial evaluated forty-two stable HD patients allocated in RS (n=22) or placebo (n=20) groups. Patients received, alternately, cookies and sachets containing 16 g/day of RS (Hi-Maize 260®) or manioc flour for four weeks. Fasting pre-dialysis blood samples were collected and IAA plasma levels measured by high performance liquid chromatography. Peripheral blood mononuclear cells were isolated and processed for AhR and nuclear factor kappa B (NF-κB) mRNA expression analyzes by quantitative real-time PCR. Anthropometric and biochemical parameters, as well as food intake were also evaluated.Results:Thirty-one patients completed the study, 15 in the RS group and 16 in the placebo group. Although there was no significant alteration in IAA plasma levels, neither in AhR mRNA expression and NF-κB mRNA expression after RS supplementation, a positive correlation (r=0.48; p=0.03) was observed between IAA plasma levels and AhR expression at baseline.Conclusion:Even though prebiotic RS supplementation did not influence IAA levels or AhR expression, their positive association reinforces a possible interaction between them.

Highlights

  • Gut microbiota imbalance is linked to high uremic toxins production such as indole-3-acetic acid (IAA) in chronic kidney disease patients

  • There was no significant difference in IAA plasma levels or in aryl hydrocarbon receptor (AhR) mRNA expression in both groups after the 4-week intervention

  • A positive correlation (r=0.48; p=0.03) was observed between IAA plasma levels and AhR mRNA expression at baseline (Figure 1)

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Summary

Introduction

Gut microbiota imbalance is linked to high uremic toxins production such as indole-3-acetic acid (IAA) in chronic kidney disease patients. This toxin can activate the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor involved with inflammation. The latest findings show that in addition to dioxins, other endogenous ligands are capable of activating it, thereby associating AhR to the various physiological pathways needed to maintain homeostasis in different tissues and cell types of animals and humans[3,4,5,6,7] Among those endogenous ligands are tryptophan metabolism-derived uremic toxins, such as indole-3-acetic acid (IAA)[8]. Uremic toxins are excreted by the kidneys, but in chronic kidney disease (CKD) their clearance is impaired, and dialysis is not able to filter them because they are strongly bounded to serum albumin[11]

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