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

Abstract

IntroductionDisruption of gut microbiota underpins some of the metabolic alterations observed in chronic kidney disease (CKD). MethodsIn a non-randomized, 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 CKD patients. The stability of microbiome and metabolome was studied during the pre-treatment phase (8 weeks), a p-inulin treatment phase (12 weeks), and a post-treatment phase (8 weeks) of the study. ResultsStudy 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. Inter-subject variations in microbiome and metabolome were larger than intra-subject 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 FDR ≤ 0.1 over phase. Specifically, there was significant enrichment in microbial metabolites derived from saccharolysis. ConclusionResults from our study highlight the stability of the gut microbiome and the expansive effect of p-inulin on microbiome and host co-metabolism in CKD patients. Findings from this study will enable rigorous design of microbiome-based intervention trials.