The effect of prebiotic consumption on gut derived uremic toxins and disease progression in rats with chronic kidney disease

This study aimed to investigate the effect of prebiotic consumption on gut derived uremic toxin levels, inflammatory and antioxidant parameters, renal damage, intestinal permeability and disease progression in rats with chronic kidney disease (CKD). Male Sprague-Dawley rats were given adenine (200 mg/kg/day) by oral gavage for 3-weeks to induce CKD. CKD rats were randomized to the prebiotic supplemented group (HP; n=9) (5g/kg/day) and non-supplemented group (HN; n=8). Also, healthy rats were randomized to the prebiotic-supplemented group (SP; n=8) (inulin, 5g/kg/day) and non-supplemented group (SN; n=8). At the end of the dietary intervention (4-weeks), all rats were euthanized and kidneys and colon were removed for histological evaluation. Serum uremic toxins- p-cresol sulphate (PCS) and indoxyl sulphate (IS), inflammation (IL-6, IL-10, TNF-α) and renal function markers (urea and creatinine) levels were evaluated. Kidney tissues were evaluated histopathologically and antioxidant markers (superoxide dismutase (SOD), glutathione peroxidase (GPx)). Also, expression level of tight-junction protein (claudin-1, occludin) were analysed in colon tissues and evaluated the intestinal barrier damage. At the end of this study, serum urea (HN: 127,4 ± 45,77; HP: 71,7 ± 17,73 mg/dl; p<0,001), PCS (HN: 1771,1 ± 762,74; HP: 632,7 ± 356,57 ng/ml; p=0,002) and IL-6 levels (HN: 205,8 ± 76,80; HP: 57,6 ± 46,80 pg/ml; p=0,001) were significantly decreased in CKD rats consuming prebiotic for 4-week. There was no significant effect of prebiotic consumption on serum creatinine, IS, IL-10 and TNF-α levels in CKD rats (p>0,05). When the histopathological changes in renal tissues were examined semi-quantitatively, it is found that the crystal accumulation, tubular and glomerular damage, tubulointerstitial fibrosis, glomerular inflammation, and total renal injury scores were less severe in the CKD group consuming prebiotic (p<0,001). GPx-activity in renal tissues was higher in the CKD-prebiotic group than in the non-supplemented group (p=0,007). However, in CKD, prebiotic consumption did not have a significant effect on SOD-activity in renal tissues(p>0,05). Significantly increased expression of the claudin-1 was observed in the descending and ascending colon tissue in both healthy and CKD groups (p>0,05). In conclusion, it is found that prebiotic supplementation for 4-weeks appeared to be associated with a reduction of serum urea, PCS, and IL-6 levels, ameliorated oxidative stress in kidney tissue, enhanced antioxidant enzyme activities in renal tissues and intestinal barrier function, and retarded CKD progression in CKD rats. Prebiotic oligofructose-enriched inulin supplementation may be an alternative dietary approach for reducing gut-derived uremic toxin formation, inflammation and intestinal barrier damage and controlling disease progression in CKD. Keywords: prebiotic, chronic kidney disease, uremic toxin, inflammation, intestinal barrier function.