Background: Indoxyl sulfate (IS) and p-cresyl sulfate (pCS), 2 important protein-bound uremic toxins, are independent risk factors for cardiovascular disease in patients with end-stage renal disease. Indole and p-cresol are gut microbiome-generated precursors of IS and pCS. Objective: The aim of the present study was to determine whether inulin-type fructans (ITFs) reduce the production of indole and p-cresol by altering their producing bacteria in patients with peritoneal dialysis. Methods: Patients receiving peritoneal dialysis for >3 mo without diabetes and not using antibiotics were recruited to a randomized, double-blind, placebo-controlled, crossover trial of ITF intervention over 36 wk (12-wk washout). The primary outcomes were gut microbiome, fecal indole and p-cresol, indole-producing bacteria, p-cresol-producing bacteria, and serum IS and pCS. The secondary outcomes were fecal pH, 24-h urine, and dialysis removal of IS and pCS. Results: Of 21 individuals randomly assigned. 15 completed the study. The daily nutrient intakes, including protein, tryptophan, and tyrosine, were isostatic during the prebiotic, washout, and placebo intervention. There were no baseline differences in the outcomes of interest between treatments. For fecal indole, its concentrations did not change significantly in either treatment. However, there was a trend toward the treatment-by-time effect (P = 0.052). with a quantitative reduction in the ITF treatment and an increase in the control. The difference in the changes between the 2 treatments was significant (-10.07 +/- 7.48 mu g/g vs +13.35 +/- 7.66 mu g/g; P = 0.040). Similar to Bacteroides thetaiotaomicron, there was a difference over time between the 2 treatments, with a significant treatment and time interaction effect (P = 0.047). There were no treatment, time, or interaction effects for fecal p-cresol, serum IS and pCS, 24-h urine. and dialysis removal of IS and pCS. Conclusions: Our results suggested that ITFs restricted the increase in gut microbiome-generated indole in patients with peritoneal dialysis. This trial was registered at http://www.chictr.org.cn/showproj.aspx?proj=21228 as ChiCTR-INR-17013739.