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.

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The results that were obtained from this model suggest that uremic serum per se does not seem to impair the integrity of intestinal epithelial cells. The increased IL-6 secretion by cells that were incubated with HD serum suggests a potential effect of uremia in the intestinal inflammatory response.

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Background and Aims According to some studies, it seems that advanced chronic kidney disease (CKD) has the potential to cause alterations in the composition of patients gut microbiota. Most of these data have been provided by comparing the microbiota profile between patients and healthy individuals. However, well-known factors that influence the microbiota composition such as age, environment and diet were not considered in the majority of these comparative studies. In the present study, we aimed to compare the gut microbiota composition between patients on peritoneal dialysis (PD) and age-paired healthy household contacts. Method This is a cross-sectional study. Patients undergoing automated PD for at least 3 months, aged 18 to 75 years and clinically stable were enrolled. Those who were using prebiotics, probiotics, symbiotics and antibiotics within a period of 30 days before the study, were not included. A healthy control group was composed by individuals living in the same home and with similar age of the patients. Participants received sterile materials to collect the feces sample and were instructed to keep it refrigerated and bring to the clinic within a period of 12h. To evaluate the microbial profile, 16S ribosomal DNA was PCR-amplified and sequenced on an IlluminaMiSeq platform. Diet was evaluated using a 3-day food record and the diet quality was analyzed by a Brazilian Diet Quality Index. Rome IV questionnaire was applied to diagnose constipation. Nutritional status was assessed by 7-point subjective global assessment (SGA) and body mass index (BMI). Fasting blood samples were collected and clinical data were obtained from interviewing the participants and from the patient’s charts. Data are presented in percentage, mean ± standard deviation or median (interquartile range). Results Twenty patients (PD group) and 20 healthy household contacts (control group) were studied. In PD group: 70% were men, 53.5 (48.2 - 66) years old, 50% had diabetes, BMI 25.9 ± 4.8 kg/m², 95% well-nourished, 40% constipated, 14 (5.2 – 43.5) months on dialysis and 80% had residual diuresis. In control group: 30% were men, 51.5 (46.2 - 59.7) years old, BMI 28.7 ± 3.5 kg/m² and 20% constipated. Except of sex (p = 0.01) and BMI (p = 0.04), there were no other differences between groups. Comparing dietary intake between groups, no difference was found in daily energy [PD: 20.8 ± 5.4 kcal/kg/d vs. control: 22.0 ± 5.6 kcal/kg/d, p = 0.51], protein (PD: 0.8 ± 0.2 g/kg/d vs. control: 0.9 ± 0.2 g/kg/d, p = 0.23) and fiber [PD: 14.1 (10.7 – 21.1) g/d vs. 13.7 (10.4 – 18.0) g/d, p = 0.85]. In addition, the Diet Quality Index was also not different between groups (PD: 52.3 ± 15.6 vs. control: 54.5 ± 14.8, p = 0.65). Regarding microbiota composition, no difference was found between groups in alfa diversity (Figure 1), beta diversity (p>0.05), and genera differential abundance (Figure 2). Conclusion In the present study, no difference in the gut microbiota composition was found between patients on PD and healthy household contacts sharing a similar environment and diet. This result suggests that CKD and PD seem not to alter significantly gut microbiota composition.