Prebiotic Administration to Chronic Kidney Disease Patients Modifies Their Fecal Microbiome and Host Metabolism

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.

We conducted a nonrandomized, open-label, three-phase pilot trial to investigate the effect of daily oral prebiotic, 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 pretreatment phase (8 weeks), p-inulin treatment phase (12 weeks), and post-treatment phase (8 weeks).

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 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 nonpolar 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.

P-inulin administration to CKD patients resulted in a distinct shift in toxin-generating proteolysis to amino acid biosynthesis and favorable changes in lipid metabolism.