Effects of Prebiotic on Metagenome and Lipid Metabolism in Patients with CKD: Findings from the TarGut CKD Study

Background: Patients with chronic kidney disease (CKD) have dysbiosis and dysmetabolism. Dysbiosis in CKD could promote progression of CKD through alterations in immune response, blood pressure regulation and metabolic changes. The aim of the study is to define the impact of p-inulin supplementation on gut microbiota-related metabolites, as well as the plasma lipid metabolism. Methods: In a non-randomized, open-label, 3-phase pilot trial, we examined the effect of oligofructose-enriched inulin (p-inulin) on functional metagenome and alterations in plasma, urine and stool metabolites in 15 patients with CKD (TarGut CKD). The study consisted of a pre-treatment phase (8 weeks), a p-inulin treatment phase (12 weeks), and a post-treatment phase (8 weeks). Results: Abundance of Bifidobacteriumadolescentis, Bifidobacterium longum and Lachnospiraceae species were increased during the treatment phase. Microbial pathways related to carbohydrate, lipid, amino acid and purine metabolism were altered during the treatment phase. Differential enrichment in microbiota generated metabolites and lipids metabolites was evident between study phases. Specifically, levels of secondary bile acids were reduced significantly in plasma, urine and stool during the treatment phase. Despite an increase in abundance of short chain fatty acid (SCFA)-producing bacteria during p-inulin consumption, there was no parallel increase in SCFA. Several polar and non-polar lipids were altered during the study phases, which was associated with specific microbiota. Conclusion: This study indicates that prebiotics alters functional metagenome, metabolic pathways and metabolites that transcends carbohydrate metabolism in patients with CKD. The clinical significance of our findings needs to be confirmed in an adequately powered clinical trial. Funding: NIDDK Support