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

Michael B Sohn; Bei Gao; Cynthia Kendrick; Anvesha Srivastava; Tamara Isakova; Jennifer J Gassman; Linda F Fried; Myles Wolf; Alfred K Cheung; Kalani L Raphael; Patricia Centron Vinales; John P Middleton; Ana Pabalan; Dominic S Raj; Pilot Studies in CKD Consortium

doi:10.1016/j.ekir.2023.12.017

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

Kidney Int Rep. 2023 Dec 30;9(3):671-685. doi: 10.1016/j.ekir.2023.12.017. eCollection 2024 Mar.

Authors

Collaborators

Pilot Studies in CKD Consortium:
Cynthia Kendrick, Tamara Isakova, Jennifer J Gassman, Linda F Fried, Myles Wolf, Alfred K Cheung, Kalani L Raphael, Joe Ix, John P Middleton, Susan Mendley, Michael F Flessner, Dominic S Raj

Affiliations

¹ Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, New York, USA.
² Division of Renal Diseases and Hypertension, George Washington University, Washington, USA.
³ School of Marine Sciences, Nanjing University of Information Science and Technology, Nanjing, China.
⁴ Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA.
⁵ Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
⁶ Division of Renal-Electrolyte, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
⁷ Division of Nephrology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA.
⁸ Division of Nephrology & Hypertension, University of Utah, Salt Lake City, Utah, USA.

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 Bifidobacterium and Anaerostipes. 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.

Keywords: Bifidobacterium; deoxycholic acid; indoles; metabolome; p-cresol; uremic toxin.