BackgroundFiber is a potential therapeutic to suppress microbiota-generated uremic molecules. This study aimed to determine if fiber supplementation decreased serum levels of uremic molecules through the modulation of gut microbiota in adults undergoing hemodialysis.MethodsA randomized, double-blinded, controlled crossover study was conducted. Following a 1-week baseline, participants consumed muffins with added pea hull fiber (PHF) (15 g/d) and control muffins daily, each for 4 weeks, separated by a 4-week washout. Blood and stool samples were collected per period. Serum p-cresyl sulfate (PCS), indoxyl sulfate (IS), phenylacetylglutamine (PAG), and trimethylamine N-oxide (TMAO) were quantified by LC–MS/MS, and fecal microbiota profiled by 16S rRNA gene amplicon sequencing and specific taxa of interest by qPCR. QIIME 2 sample-classifier was used to discover unique microbiota profiles due to the consumption of PHF.ResultsIntake of PHF contributed an additional 9 g/d of dietary fiber to the subjects’ diet due to compliance. No significant changes from baseline were observed in serum PCS, IS, PAG, or TMAO, or for the relative quantification of Akkermansia muciniphila, Faecalibacterium prausnitzii, Bifidobacterium, or Roseburia, taxa considered health-enhancing. Dietary protein intake and IS (r = −0.5, p = 0.05) and slow transit stool form and PCS (r = 0.7, p