Research Viewpoints Therapy of Experimental CKD with Synbiotics

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Iwashita Y, Ohya M, Yashiro M, Sonou T, Kawakami K, Nakashima Y, Yano T, Iwashita Y, Mima T, Negi S, Kubo K, Tomoda K, Odamaki T, Shigematsu T: Dietary Changes Involving Bifidobacterium Longum and Other Nutrients Delay CKD Progression. Am J Nephrol 2018;47:325–332

The intestinal microbiome has become a facet of human biology that is attracting great interest, including among investigators in the field of kidney disease. In CKD, “uremic” toxins may be elaborated by the action of intestinal microbiota on dietary constituents (dysbiosis). Altering the composition of the bacterial flora of the intestine may have therapeutic potential, but this is a very challenging area of clinical investigation.

Iwashita and co-workers conducted an experimental study of gut microbiota in 5/6th nephrectomized rats and sham-operated controls. Combined treatment (for 8 weeks) with pre-biotics (glutamine, fiber and oligosaccharides) and probiotics (bifidobacterium longum), or “synbiotic” therapy (also called GFOB diets) were examined. Gut microbiota as assessed by stool DNA analysis was altered in the nephrectomized rats compared to controls and the synbiotic diets tended to reverse these abnormalities. Indoxyl sulfate levels in the serum were reduced by the synbiotic treatment. Serum creatinine, inorganic phosphate, calcium, iPTH but not FGF23 levels were lower in the synbiotic treated nephrectomized rats compared to controls. Tubulo-interstitial injury was modestly less in the synbiotic treated nephrectomized rats compared to controls. See Figure:

Tubulointerstitial injury. a Histological images of tubulointerstitial injury by PAS staining and (b) tubulointerstitial injury score in each group. Nx and diet effects were significantly different when analyzed using 2-way ANOVA. Scale bars: 50 μm. PAS, periodic acid–Schiff; Sham, sham-operated; Nx, nephrectomy; CON, control; ANOVA, analysis of variance. (From: Am J Nephrol 2018;47:325-332)

These preliminary findings provide some encouragement for pursuit of similar studies in humans with CKD, but whether the mechanism(s) of the demonstrated beneficial effects are actually due to the induced changes in gut microbiota cannot be determined. Pair-feeding, estimations of total nitrogen intake and excretion, and blood pressure alterations were not examined in the experimental design. Much more work is required to see if this “synbiotic” therapeutic approach to modify the course of CKD in human is valid. This preliminary study is novel and interesting, but incomplete.