Resistant starch supplementation effects on plasma indole 3-acetic acid and aryl hydrocarbon receptor mRNA expression in hemodialysis patients: Randomized, double blind and controlled clinical trial

Abstract

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. 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.

Effects of Probiotics, Prebiotics, and Synbiotics on Uremic Toxins, Inflammation, and Oxidative Stress in Hemodialysis Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…The hemodialysis duration of all participants with mean age ranging from 32 to 63 years is presented in Table 1 . The shortest duration of intervention was 4 weeks [ 20 , 21 , 22 , 23 ], and the longest was 24 weeks [ 24 , 25 ].…”

Food-Derived Uremic Toxins in Chronic Kidney Disease

“…An inverse correlation was found between serum-free indole-3-acetic acid and free indoxyl sulfate with fiber consumption in children with CKD [ 132 ]. However, a supplementation of resistant starch, a type of fiber, to CKD patients on hemodialysis did not lead to a decrease in the indole-3-acetic acid plasma level [ 133 ].Of note, indole-3-acetic acid was recently shown to be produced by the host, specifically in immune cells possessing the interleukin-4-induced gene 1 (IL4I1), which encodes a protein that converts tryptophan, phenylalanine, and tyrosine [ 134 ]. It remains unclear to which extent the host production contributes to the plasma level.…”

Natural products from plants and microorganisms: Novel therapeutics for chronic kidney disease via gut microbiota regulation

“…In a clinical trial of 60 peritoneal dialysis patients, Shen-Shuai-Ning granules could decrease IS serum concentration after 12 weeks of treatment ( Chen et al, 2018 ). Supplementation with the functional food HI-MAIZE ® 260 cookies (16 g/d resistant starch) could increase fiber intake, reduce IL-6 and IS plasma levels ( Esgalhado et al, 2018 ), decrease different growth factors ( De Paiva et al, 2020 ), and alter the SCFA-producing microbiota in HD patients ( Kemp et al, 2021 ), but no indole-3-acetic acid (IAA) levels or aryl hydrocarbon receptor (AhR) expression in patients with end-stage CKD ( Azevedo et al, 2020 ). However, the unripe banana flour (21 g/d, 48% resistant starch) only decreased IS in the subgroup of participants undergoing peritoneal dialysis (PD) ( De Andrade et al, 2021 ).…”