Effect of a prebiotic (fructooligosacharide) on uremic toxins of chronic kidney disease patients

Abstract

Intestinal microbiome has been considered a new therapeutic target for chronic kidney disease (CKD) due to its potential role on the metabolic disturbances associated to the disease. The abnormalities in the microbiota, frequently found in patients with CKD, contribute to the accumulation of uremic toxins derived from the unbalanced fermentation of nitrogen compounds in relation to the non-digestible carbohydrates. Among them, p-cresyl sulfate and indoxyl sulfate have been associated with inflammation, kidney disease progression, cardiovascular dysfunction and increased risk of death in this population of patients. Besides restriction of dietary protein, a well-established therapy for reducing uremic toxicity, other dietary approaches such as the use of prebiotics, probiotics and symbiotic may represent a promising intervention due to their beneficial effect as modulators of the intestinal microbiota. Preliminary short-term studies with patients undergoing dialysis have shown that such intervention promoted reduction in the serum concentration of p-cresyl sulfate or indoxyl sulfate. In comparison with probiotics, prebiotics have the advantage to stimulate the host's microbiota and to occur naturally in several foods. In the context of CKD the use of prebiotics has been poorly investigated. Therefore, the primary aim of this study is to investigate the effect of a prebiotic (fructooligoschadaride -FOS) on serum and urinary levels of p-cresyl sulfate and indoxyl sulfate of non-dialysis dependent patients with CKD. As a secondary aim we will investigate the impact of such intervention on serum markers intestinal permeability, endotoxemia and inflammatory response. This is a 12-week double-blind randomized controlled clinical trial. Fifty non-diabetic patients with CKD stages 4 and 5 were randomly assigned to a 12 g/day of the prebiotic (FOS) or placebo (maltodextrine). All patients have already been randomized and the end of data collection is planned to finish in November, 2016. A similar ongoing project, but evaluating the effect of a symbiotic (SYNERGY - SYnbiotics Easing Renal failure by Improving Gut Microbiology), is developed by the Australian group coordinated by Professor Katrina Campbell. This group is internationally recognized by the experience and quality of their projects in this area. Therefore, the purpose of the fellowship is to expand the knowledge and to contribute with qualification of the candidate in the research area, by exchanging experience with an expert researcher in nutrition and chronic kidney disease. The fellowship will narrow the relationship between the Brazilian and Australian groups in order to contribute with future collaboration. During the fellowship the candidate will perform the analysis of her thesis results and submit at least one paper for publication. The candidate will also contribute with analysis and/or drafting process of the projects developed by the Australian group, to follow and to assist in the SINERGY II data collection, particularly the performance of microbiome analysis (DNA sequencing, culture, and related "omics" measures). (AU)