Prebiotics improve metabolic parameter in uremic mice by reducing intestinal production of p-cresyl sulfate

Abstract

Chronic kidney disease (CKD) is associated with a large range of metabolic alterations. P-cresyl sulfate (PCS) has been identified as one of the main uremic toxins involved in the pathogenesis of accelerated atherosclerosis in CKD. The prebiotic soluble fibers have the property of selectively stimulate growth and activity of a limited number of beneficial bacteria in the colon. The aim of this study is to assess in mice the effects of prebiotics by the reduction of PCS intestinal production, on metabolic disturbances associated with CKD. Subtotally nephrectomized C57BL/6J wild-type mice were divided into two groups: CKD mice and CKD mice fed with 5% (w/w standard diet) of prebiotic arabinoxylane oligosaccharides (AXOS, WITAXOS SA,). Three weeks after initiation of prebiotics serum cholesterol total, triglycerides, glucose, PCS were measured. The insulin sensitivity was estimated by intra-peritoneal insulin tolerance test and glucose tolerance test. CKD mice treated with AXOS exhibited a significant decrease in serum total PCS (−74%, p=0.03). Prebiotic treatment reduced the loss of fat mass observed in CKD (+33%, p<0.05). and prevented the ectopic lipid redistribution associated with CKD. Prebiotic treatment completely prevented the expected increase in glycemia, total cholesterol and triglycerides associated with CKD. Insulin sensitivity was significantly improved in prebiotic group. These results suggest that prebiotics AXOS decrease PCS and prevented CKD-induced insulin resistance, the loss of adipose tissue and prevented accumulation of ectopic lipids in muscle and liver.. Because insulin resistance is an important cardiovascular risk factor, novel therapeutic approaches like prebiotics which could decrease PCS and cardio vascular mortality.