Prebiotic Administration to CKD Patients Modifies Their Microbiome and Metabolism

Dominic S. Raj, Division of Renal Diseases and Hypertension, George Washington University, Washington DC, USA.
Bei Gao, Division of Renal Diseases and Hypertension, George Washington University, Washington DC, USA; School of Marine Sciences, Nanjing University of Information Science and Technology, Nanjing, China, 210044. Electronic address: draj@mfa.gwu.edu.
Michael B. Sohn, Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, New York.
Christopher Brydges, UC Davis Genome Center - Metabolomics, University of California, Davis, CA.
Anvesha Srivastava, Division of Renal Diseases and Hypertension, George Washington University, Washington DC, USA.
Hamid Rabb, Division of Nephrology, Johns Hopkins University, Baltimore, Maryland, USA.
Alfred K. Cheung, Division of Nephrology & Hypertension, University of Utah, Salt Lake City, Utah.
Oliver Fiehn, UC Davis Genome Center - Metabolomics, University of California, Davis, CA.
Cynthia Kendrick, Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio.
Jennifer J. Gassman, Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio.
Anam Tariq, Division of Renal Diseases and Hypertension, George Washington University, Washington DC, USA.
Tamara Isakova, Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Linda F. Fried, Renal Section, VA Pittsburgh Healthcare System and Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Myles Wolf, Division of Nephrology, Duke University School of Medicine, Durham, North Carolina.
Kalani L. Raphael, Division of Nephrology & Hypertension, University of Utah, Salt Lake City, Utah.
John P. Middleton, Division of Nephrology, Duke University School of Medicine, Durham, North Carolina.
Yoosif Abdalla, Division of Renal Diseases and Hypertension, George Washington University, Washington DC, USA.

Document Type

Journal Article

Publication Date

11-21-2025

Journal

Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation

DOI

10.1053/j.jrn.2025.10.015

Keywords

Amino acid metabolism; Dysbiosis; Short chain fatty acids; Uremic toxins; lipid metabolism; lipidome and Deoxycholic acid; p-inulin

Abstract

BACKGROUND AND HYPOTHESIS: Prebiotics are believed to improve gut microbial dysbiosis and dysmetabolism in chronic kidney disease (CKD) patients. However, impact of prebiotics on gut microbial metagenome and dynamic changes in metabolome has not been clearly defined. METHODS: We conducted a non-randomized, open-label, three-phase pilot trial, to investigate the effect of daily oral oligofructose-enriched inulin (p-inulin) on stool functional metagenome and changes in plasma, urine and stool metabolites in 13 CKD patients. The study comprised a pre-treatment phase (8 weeks), p-inulin treatment phase (12 weeks), and post-treatment phase (8 weeks). RESULTS: During treatment phase, there was a significant increase in the abundance of Bifidobacterium adolescentis, Bifidobacterium longum, and Lachnospiraceae species. Microbial pathways related to carbohydrate degradation and amino acid biosynthesis were enriched during the treatment phase, but urea biosynthetic pathway was attenuated. In the plasma metabolic biosynthetic pathways for valine, leucine and isoleucine were activated during the treatment phase. Microbial genes related to lipid metabolism were enriched during post-treatment. Abundance of several polar and non-polar lipids were altered in plasma and stool samples during treatment and post-treatment phases. Pathway analysis for lipids indicated suppression of triglyceride biosynthesis in plasma and enhanced triglyceride degradation in stool during the treatment phase. Secondary bile acid levels in plasma, urine and stool were significantly reduced during p-inulin consumption. Urine levels of indoxyl sulfate and p-cresol sulfate were reduced during treatment phase. CONCLUSION: P-inulin administration to CKD patients resulted a distinct shift in toxin-generating proteolysis to amino acid biosynthesis and favorable changes in lipid metabolism.

Department

Medicine

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