Targeting Gut Microbiome With Prebiotic in Patients With CKD: The TarGut-CKD Study

Michael B. Sohn, Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, New York, USA.
Bei Gao, Division of Renal Diseases and Hypertension, George Washington University, Washington, USA.
Cynthia Kendrick, Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA.
Anvesha Srivastava, Division of Renal Diseases and Hypertension, George Washington University, Washington, USA.
Tamara Isakova, Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Jennifer J. Gassman, Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA.
Linda F. Fried, Division of Renal-Electrolyte, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Myles Wolf, Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
Alfred K. Cheung, Division of Nephrology & Hypertension, University of Utah, Salt Lake City, Utah, USA.
Kalani L. Raphael, Division of Nephrology & Hypertension, University of Utah, Salt Lake City, Utah, USA.
Patricia Centron Vinales, Division of Renal Diseases and Hypertension, George Washington University, Washington, USA.
John P. Middleton, Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
Ana Pabalan, Division of Renal Diseases and Hypertension, George Washington University, Washington, USA.
Dominic S. Raj, Division of Renal Diseases and Hypertension, George Washington University, Washington, USA.

Document Type

Journal Article

Publication Date

3-1-2024

Journal

Kidney international reports

Volume

9

Issue

3

DOI

10.1016/j.ekir.2023.12.017

Keywords

Bifidobacterium; deoxycholic acid; indoles; metabolome; p-cresol; uremic toxin

Abstract

INTRODUCTION: Disruption of gut microbiota underpins some of the metabolic alterations observed in chronic kidney disease (CKD). METHODS: In a nonrandomized, open-label, 3-phase pilot trial, with repeated measures within each phase, we examined the efficacy of oligofructose-enriched inulin (p-inulin) in changing the gut microbiome and their metabolic products in 15 patients with CKD. The stability of microbiome and metabolome was studied during the pretreatment phase (8 weeks), a p-inulin treatment phase (12 weeks), and a post treatment phase (8 weeks) of the study. RESULTS: Study participants completed 373 of the 420 expected study visits (88.8%). Adherence to p-inulin was 83.4%. 16S rRNA sequencing was performed in 368 stool samples. A total of 1085 stool, urine, and plasma samples were subjected to untargeted metabolomic studies. p-inulin administration altered the composition of the gut microbiota significantly, with an increase in abundance of and . Intersubject variations in microbiome and metabolome were larger than intrasubject variation, indicating the stability of the gut microbiome within each phase of the study. Overall metabolite compositions assessed by beta diversity in urine and stool metabolic profiles were significantly different across study phases. Several specific metabolites in stool, urine, and plasma were significant at false discovery rate (FDR) ≤ 0.1 over phase. Specifically, there was significant enrichment in microbial metabolites derived from saccharolysis. CONCLUSION: Results from our study highlight the stability of the gut microbiome and the expansive effect of p-inulin on microbiome and host cometabolism in patients with CKD. Findings from this study will enable rigorous design of microbiome-based intervention trials.

Department

Medicine

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