Author:
Raj Dominic S.,Sohn Michael B.,Charytan David M.,Himmelfarb Jonathan,Ikizler T. Alp,Mehrotra Rajnish,Ramezani Ali,Regunathan-Shenk Renu,Hsu Jesse Y.,Landis J. Richard,Li Hongzhe,Kimmel Paul L.,Kliger Alan S.,Dember Laura M.,
Abstract
BackgroundThe intestinal microbiome is an appealing target for interventions in ESKD because of its likely contribution to uremic toxicity. Before conducting clinical trials of microbiome-altering treatments, it is necessary to understand the within-person and between-person variability in the composition and function of the gut microbiome in patients with ESKD.MethodsWe conducted a multicenter, nonrandomized, crossover feasibility study of patients on maintenance hemodialysis consisting of three phases: pretreatment (8 weeks); treatment, during which the prebiotic, p-inulin, was administered at a dosage of 8 g twice daily (12 weeks); and post-treatment (8 weeks). Stool samples were collected 1–2 times per week and blood was collected weekly for 28 weeks. The gut microbiome was characterized using 16S ribosomal-RNA sequencing and metabolomic profiling.ResultsA total of 11 of the 13 participants completed the 28-week study. Interparticipant variability was greater than intraparticipant variability for microbiome composition (P<0.001 by UniFrac distances) and metabolomic composition (P<0.001 by Euclidean distances). p-Inulin was well tolerated by 12 of 13 participants. Adherence to the frequent sample collection and self-aliquoting of stool samples were both 96%. A change in the microbiome composition from pretreatment to post-treatment was evident by the overall shifts in weighted UniFrac distances (P=0.004) and a progressive decrease in prevalence of high intraclass correlations, indicating an increase in intraparticipant microbiome diversity during and after p-inulin treatment. An effect of p-inulin on the metabolomic profile was not evident.ConclusionsThe intraparticipant stability of the gut microbiome under no-treatment conditions, the tolerability of p-inulin, the signals of increased diversity of the microbiome with p-inulin treatment, and the willingness of participants to provide stool samples all support the feasibility of a larger trial to investigate interventions targeting the gut microbiome in patients with ESKD. Whether or not p-inulin has sufficient efficacy as an intervention requires evaluation in larger studies.Clinical Trial registry name and registration number:Gut Microbiome and p-Inulin in Hemodialysis, NCT02572882
Funder
National Institute of Diabetes and Digestive and Kidney Diseases
Publisher
American Society of Nephrology (ASN)
Cited by
3 articles.
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