Effects of prebiotic oligofructose-enriched inulin on gut-derived uremic toxins and disease progression in rats with adenine-induced chronic kidney disease.

Oguz Kul,Gulhan Samur,Francois Blachier,Ebru Melekoglu,M Alper Cetinkaya,S Evrim Kepekci-Tekkeli

doi:10.1371/journal.pone.0258145

Oguz Kul, Gulhan Samur + Show 4 more

Open Access

https://doi.org/10.1371/journal.pone.0258145

Copy DOI

Journal: PloS one	Publication Date: Oct 6, 2021
Citations: 9	License type: CC BY 4.0

Affiliation: Hacettepe University

Abstract

Recent studies suggest that dysbiosis in chronic kidney disease (CKD) increases gut-derived uremic toxins (GDUT) generation, leads to systemic inflammation, reactive oxygen species generation, and poor prognosis. This study aimed to investigate the effect of oligofructose-enriched inulin supplementation on GDUT levels, inflammatory and antioxidant parameters, renal damage, and intestinal barrier function in adenine-induced CKD rats. Male Sprague-Dawley rats were divided into control group (CTL, n = 12) fed with standard diet; and CKD group (n = 16) given adenine (200 mg/kg/day) by oral gavage for 3-weeks to induce CKD. At the 4th week, CKD rats were subdivided into prebiotic supplementation (5g/kg/day) for four consecutive weeks (CKD-Pre, n = 8). Also, the control group was subdivided into two subgroups; prebiotic supplemented (CTL-Pre, n = 6) and non-supplemented group (CTL, n = 6). Results showed that prebiotic oligofructose-enriched inulin supplementation did not significantly reduce serum indoxyl sulfate (IS) but did significantly reduce serum p-Cresyl sulfate (PCS) (p = 0.002) in CKD rats. Prebiotic supplementation also reduced serum urea (p = 0.008) and interleukin (IL)-6 levels (p = 0.001), ameliorated renal injury, and enhanced antioxidant enzyme activity of glutathione peroxidase (GPx) (p = 0.002) and superoxide dismutase (SOD) (p = 0.001) in renal tissues of CKD rats. No significant changes were observed in colonic epithelial tight junction proteins claudin-1 and occludin in the CKD-Pre group. In adenine-induced CKD rats, oligofructose-enriched inulin supplementation resulted in a reduction in serum urea and PCS levels, enhancement of the antioxidant activity in the renal tissues, and retardation of the disease progression.

Highlights

Chronic kidney disease (CKD) is characterized by progressive glomerular, tubular, and interstitial damage, in which case metabolic end products, called uremic toxins, accumulate in the body [1]
There was no significant difference in body weight between the CKD and CKD rats with prebiotic diet (CKD-Pre) (p = 0.06), and between control rats with normal diet (CTL) and control rats with prebiotic diet (CTL-Pre) groups (p = 0.238)
As kidney function becomes less effective, uremic toxins accumulate in the body, with those are thought to be responsible for inflammation, gut dysbiosis, bacterial translocation, and CKD progression [20]

Summary

Introduction

Chronic kidney disease (CKD) is characterized by progressive glomerular, tubular, and interstitial damage, in which case metabolic end products, called uremic toxins, accumulate in the body [1]. The uremic state in CKD causes increased generation of gut-derived uremic toxins (GDUT) such as indoxyl sulfate (IS) and p-Cresyl sulfate (PCS) as a consequence of changes in gut microbiota composition and metabolism [2]. Gut dysbiosis in patients with CKD has multifactorial causes including uremic state, metabolic acidosis, pharmacological therapies (antibiotics, phosphate binders), slow colonic transit, and dietary restriction of potassium-rich fruits and vegetables [4, 5]. Low dietary fiber intake can increase intestinal permeability, transportation of endotoxins via the circulatory system, and chronic inflammation and aggravate CKD progression [2, 7]

Objectives

Methods

Results

Conclusion