Dominic S Raj1, Michael B Sohn2, David M Charytan3, Jonathan Himmelfarb4, T Alp Ikizler5, Rajnish Mehrotra6, Ali Ramezani1, Renu Regunathan-Shenk1, Jesse Y Hsu7, J Richard Landis7, Hongzhe Li7, Paul L Kimmel8, Alan S Kliger9, Laura M Dember10. 1. Division of Renal Diseases and Hypertension, George Washington University School of Medicine, Washington, DC. 2. Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, New York. 3. Division of Nephrology, Department of Medicine, New York University Grossman School of Medicine, New York, New York. 4. Division of Nephrology, Department of Medicine, Kidney Research Institute, University of Washington, Seattle, Washington. 5. Division of Nephrology and Hypertension, Department of Medicine, and Vanderbilt Center for Kidney Disease, Vanderbilt University Medical Center, Nashville, Tennessee. 6. Division of Nephrology, Department of Medicine, Kidney Research Institute and Harborview Medical Center, University of Washington, Seattle, Washington. 7. Department of Biostatistics, Epidemiology and Informatics, and Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 8. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland. 9. Department of Medicine, Yale School of Medicine, New Haven, Connecticut. 10. Renal-Electrolyte and Hypertension Division, Department of Medicine, and Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Abstract
Background: The 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. Methods: We 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. Results: A 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. Conclusions: The 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.
Background: The 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. Methods: We 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. Results: A 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. Conclusions: The 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.
Authors: Colin Hill; Francisco Guarner; Gregor Reid; Glenn R Gibson; Daniel J Merenstein; Bruno Pot; Lorenzo Morelli; Roberto Berni Canani; Harry J Flint; Seppo Salminen; Philip C Calder; Mary Ellen Sanders Journal: Nat Rev Gastroenterol Hepatol Date: 2014-06-10 Impact factor: 46.802
Authors: Ruben Poesen; Pieter Evenepoel; Henriette de Loor; Jan A Delcour; Christophe M Courtin; Dirk Kuypers; Patrick Augustijns; Kristin Verbeke; Björn Meijers Journal: PLoS One Date: 2016-04-21 Impact factor: 3.240
Authors: Bei Gao; Hui-Wen Lue; Jennifer Podolak; Sili Fan; Ying Zhang; Archana Serawat; Joshi J Alumkal; Oliver Fiehn; George V Thomas Journal: Metabolites Date: 2019-04-26