Pea hull fiber supplementation modulates gut microbiota composition but not uremic metabolites in adults receiving hemodialysis: A randomized, double-blind, controlled trial

Background: Fiber 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. Methods: A 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 and when merged with 16S profiles of non-dialysis adults. Results: 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 < 0.01) were significantly correlated at baseline. Taxa that most distinguished the microbiota composition during the PHF periods were enriched Gemmiger, Collinsella, and depleted Lactobacillus, Ruminococcus, Coprococcus, and Mogibacteriaceae. Compared to non-dialysis cohorts, dialysis patients showed a lower abundance of Faecalibacterium, Lachnospira, and Peptostreptococcaceae, and higher Eggerthella and Collinsella, previously reported markers of kidney disease, as well as Rikenellaceae, Granulicatella, Oscillospira, Coprobacillus, Ruminococcus, and Rothia. Conclusion: Although PHF supplementation modulated fecal microbiota composition, serum levels of targeted uremic molecules remained unchanged. A higher fiber dose or alternative sources of fiber may be needed to exhibit efficacy. The results of this study support the premise that dialysis patients exhibit a microbiota profile that differs from non-dialysis cohorts