Galacto-oligosaccharides attenuate renal injury with microbiota modification

Abstract

AbstractsTubulointerstitial injury is central to the progression of end‐stage renal disease. Recent studies have revealed that one of the most investigated uremic toxins, indoxyl sulfate (IS), caused tubulointerstitial injury through oxidative stress and endoplasmic reticulum (ER) stress. Because indole, the precursor of IS, is synthesized from dietary tryptophan by the gut microbiota, we hypothesized that the intervention targeting the gut microbiota in kidney disease with galacto‐oligosaccharides (GOS) would attenuate renal injury. After 2 weeks of GOS administration for 5/6 nephrectomized (Nx) or sham‐operated (Sham) rats, cecal indole and serum IS were measured, renal injury was evaluated, and the effects of GOS on the gut microbiota were examined using pyrosequencing methods. Cecal indole and serum IS were significantly decreased and renal injury was improved with decreased infiltrating macrophages in GOS‐treated Nx rats. The expression levels of ER stress markers and apoptosis were significantly increased in the Nx rats and decreased with GOS. The microbiota analysis indicated that GOS significantly increased three bacterial families and decreased five families in the Nx rats. In addition, the analysis also revealed that the bacterial family Clostridiaceae was significantly increased in the Nx rats compared with the Sham rats and decreased with GOS. Taken altogether, our data show that GOS decreased cecal indole and serum IS, attenuated renal injury, and modified the gut microbiota in the Nx rats, and that the gut microbiota were altered in kidney disease. GOS could be a novel therapeutic agent to protect against renal injury.

Dietary Changes Involving <b><i>Bifidobacterium</i></b> <b><i>longum</i></b> and Other Nutrients Delays Chronic Kidney Disease Progression

“…Studies report that prebiotic and/or probiotic treatments results in decreases in uremic toxins such as indoxyl sulfate and p-cresol in humans and animals by improving the gut environment [9, 14]. Additionally, it is reported that prebiotic and/or probiotic treatments ameliorate kidney function in humans and animals by improving the gut environment [24, 25].…”

“…The SCFA produced by bacteria are the major source of energy for colonocytes [27]. Furuse et al [14] reported that the proportion of Bifidobacteriaceae was significantly increased and Ruminococcaceae was decreased in Nx GOS (administration of galacto-oligosaccharides) rats compared with Nx CON rats. Our data were similar to their results in that Bifidobacterium was significantly increased in Nx GFOB rats compared with Nx CON rats.…”

“…Semi-quantitative evaluation of tubulointerstitial injury was performed in a blinded manner using > 15 randomly selected regions of the cortex [13]. Tubulointerstitial injury was graded based on the percentage of tubular cellularity, basement membrane thickening, cell infiltration, tubular dilation, atrophy, sloughing, or interstitial widening as: 0, no change; 1, < 10% injury; 2, 10–25% injury; 3, 25–50% injury; 4, 50–75% injury; 5, 75–100% injury [14]. …”

Role of Gut-Derived Protein-Bound Uremic Toxins in Cardiorenal Syndrome and Potential Treatment Modalities

“…In 5/6 nephrectomized rats, 2 weeks administration of galacto-oligosaccharides can modify the gut microbiota by increasing 3 bacterial families and decreasing 5 bacterial families, including Clostridiaceae. 90 This finding is associated with a reduction in serum IS levels, cecal indole, endoplasmic reticulum stress and apoptosis, and an improvement of renal injury. 90 A non-randomized phase I/II study of hemodialysis patients demonstrated that administration of prebiotic oligofructose-enriched inulin for 4 weeks significantly reduced serum levels of pCS, but not IS.…”

“…90 This finding is associated with a reduction in serum IS levels, cecal indole, endoplasmic reticulum stress and apoptosis, and an improvement of renal injury. 90 A non-randomized phase I/II study of hemodialysis patients demonstrated that administration of prebiotic oligofructose-enriched inulin for 4 weeks significantly reduced serum levels of pCS, but not IS. 91 Synbiotics "Synbiotic" treatment uses a combination of probiotics and prebiotics.…”