The Effect of ß-Glucan Prebiotic on Kidney Function, Uremic Toxins and Gut Microbiome in Stage 3 to 5 Chronic Kidney Disease (CKD) Predialysis Participants: A Randomized Controlled Trial

Abstract

There is growing evidence that gut dysbiosis contributes to the progression of chronic kidney disease (CKD) owing to several mechanisms, including microbiota-derived uremic toxins, diet and immune-mediated factors. The aim of this study was to investigate the effect of a ß-glucan prebiotic on kidney function, uremic toxins and the gut microbiome in stage 3 to 5 CKD participants. Fifty-nine participants were randomized to either the ß-glucan prebiotic intervention group (n = 30) or the control group (n = 29). The primary outcomes were to assess kidney function (urea, creatinine and glomerular filtration rate), plasma levels of total and free levels of uremic toxins (p-cresyl sulfate (pCS), indoxyl-sulfate (IxS), p-cresyl glucuronide (pCG) and indoxyl 3-acetic acid (IAA) and gut microbiota using 16S rRNA sequencing at baseline, week 8 and week 14. The intervention group (age 40.6 ± 11.4 y) and the control group (age 41.3 ± 12.0 y) did not differ in age or any other socio-demographic variables at baseline. There were no significant changes in kidney function over 14 weeks. There was a significant reduction in uremic toxin levels at different time points, in free IxS at 8 weeks (p = 0.003) and 14 weeks (p < 0.001), free pCS (p = 0.006) at 14 weeks and total and free pCG (p < 0.001, p < 0.001, respectively) and at 14 weeks. There were no differences in relative abundances of genera between groups. Enterotyping revealed that the population consisted of only two of the four enterotypes: Bacteroides 2 and Prevotella. The redundancy analysis showed a few factors significantly affected the gut microbiome: these included triglyceride levels (p < 0.001), body mass index (p = 0.002), high- density lipoprotein (p < 0.001) and the prebiotic intervention (p = 0.002). The ß-glucan prebiotic significantly altered uremic toxin levels of intestinal origin and favorably affected the gut microbiome.

Keywords: chronic kidney disease (CKD); gut microbiome; prebiotic; uremic toxins.

Figure 1

CONSORT flow diagram on the effects of a ß-glucan prebiotic on kidney function, plasma levels of uremic toxins and the gut microbiome in predialysis participants with CKD stage 3 to 5.

Figure 2

Schematic representation of the study flow; Nutrition status includes anthropometry, clinical, dietary assessment, other nutrition-related biochemical tests.

Figure 3

Relative abundances at the genera level.

Figure 4

Enterotype percentages of the intervention and control group over time.

Figure 5

Alpha and beta diversity comparisons by groups. (A) Principal coordinate analysis (PCoA2) of inter-individual differences (beta diversity) by Bray–Curtis dissimilarity. (B) Alpha diversity according to the Shannon index. (C) Within-group inter-individual Bray–Curtis distance.

Figure 6

Cumulative effect size of covariates affecting the compositional variation of the gut microbiome selected by the redundancy analysis (grey bars) compared with individual effect sizes assuming independence (black bars).