Abstract
In chronic kidney disease (CKD), the accumulation of gut-derived metabolites, such as indoxyl sulfate (IS), p-cresyl sulfate (pCS), and indole 3-acetic acid (IAA), has been associated with the burden of the disease. In this context, prebiotics emerge as a strategy to mitigate the accumulation of such compounds, by modulating the gut microbiota and production of their metabolites. The aim of this study was to evaluate the effect of unripe banana flour (UBF—48% resistant starch, a prebiotic) on serum concentrations of IS, pCS, and IAA in individuals undergoing peritoneal dialysis (PD). A randomized, double-blind, placebo-controlled, crossover trial was conducted. Forty-three individuals on PD were randomized to sequential treatment with UBF (21 g/day) and placebo (waxy corn starch—12 g/day) for 4 weeks, or vice versa (4-week washout). The primary outcomes were total and free serum levels of IS, pCS, and IAA. Secondary outcomes were 24 h urine excretion and dialysis removal of IS, pCS, and IAA, serum inflammatory markers [high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α)], serum lipopolysaccharide LPS, and dietary intake. Of the 43 individuals randomized, 26 completed the follow-up (age = 55 ± 12 years; 53.8% men). UBF did not promote changes in serum levels of IS (p = 0.70), pCS (p = 0.70), and IAA (p = 0.74). Total serum IS reduction was observed in a subgroup of participants (n = 11; placebo: median 79.5 μmol/L (31–142) versus UBF: 62.5 μmol/L (31–133), p = 0.009) who had a daily UBF intake closer to that proposed in the study. No changes were observed in other secondary outcomes. UBF did not promote changes in serum levels of IS or pCS and IAA; a decrease in IS was only found in the subgroup of participants who were able to take 21g/day of the UBF.
Highlights
Numerous metabolites that normally are part of the mammalian serum metabolome are derived from the metabolism of the gut microbiota [1,2]
We found that supplementation with unripe banana flour (UBF) for 4 weeks did not affect either the serum levels of indoxyl sulfate (IS) or p-cresyl sulfate (pCS) and indole 3-acetic acid (IAA)
We found that the UBF did not affect either the serum levels of IS or pCS and IAA
Summary
Numerous metabolites that normally are part of the mammalian serum metabolome are derived from the metabolism of the gut microbiota [1,2]. The fermentation of tryptophan results in indole and IAA and the result of tyrosine fermentation is p-cresol. In chronic kidney disease (CKD), due to gradual loss of kidney function, several compounds are retained, including those derived from the gut microbiome. Serum concentration of these compounds increases gradually as renal function decreases, reaching the highest level in dialysis [7,8]. Since they are bounded to serum protein, their dialytic clearance is low [8,9]. Accumulation of these uremic toxins has been associated with the progression of CKD [10], inflammation [11,12], cardiovascular disease [13,14], and mortality from cardiovascular disease and all causes in individuals with CKD [15,16,17]
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