Abstract

We aimed to develop an innovative synbiotic formulation for use in reducing dysbiosis, uremic toxins (e.g., p-cresol and indoxyl sulfate), and, consequently, the pathognomonic features of patients with chronic kidney disease (CKD). Twenty-five probiotic strains, belonging to lactobacilli and Bifidobacterium, were tested for their ability to grow in co-culture with different vegetable (pomegranate, tomato, and grapes) sources of antioxidants and prebiotics (inulin, fructo-oligosaccharides, and β-glucans). Probiotics were selected based on the acidification rates and viable cell counts. Inulin and fructo-oligosaccharides reported the best prebiotic activity, while a pomegranate seed extract was initially chosen as antioxidant source. The investigation was also conducted in fecal batches from healthy and CKD subjects, on which metabolomic analyses (profiling volatile organic compounds and total free amino acids) were conducted. Two out of twenty-five probiotics were finally selected. After the stability tests, the selective innovative synbiotic formulation (named NatuREN G) comprised Bifidobacterium animalis BLC1, Lacticaseibacillus casei LC4P1, fructo-oligosaccharides, inulin, quercetin, resveratrol, and proanthocyanidins. Finally, NatuREN G was evaluated on fecal batches collected from CKD in which modified the viable cell densities of some cultivable bacterial patterns, increased the concentration of acetic acid and decane, while reduced the concentration of nonanoic acid, dimethyl trisulfide, and indoxyl sulfate.

Highlights

  • Chronic kidney disease (CKD) refers to damaged kidneys with decreased capability to filter blood

  • Compared with the wild type (WT), the presence of high levels of polyphenols in all the transgenic varieties (Indigo, ResTom, and Bronze) agree with the antioxidant activity of the hydrophilic fractions extracted from ripe fruits, with Bronze showing the highest activity (Supplementary Table S1)

  • This study provides evidence that the innovative synbiotic NatuREN G may be able to decrease the level of uremic toxins, at least under in vitro conditions simulating dysbiosis and some of the pathognomonic characteristics linked to nephropathy

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Summary

Introduction

Chronic kidney disease (CKD) refers to damaged kidneys with decreased capability to filter blood. CKD can evolve into end-stage-renal disease (ESRD), where the kidneys do not work, necessitating dialysis [1,2]. An altered kidney functionality determines an excess of waste metabolites that, accumulating in blood, causes other health problems, such as heart disease and stroke [3]. The incidence of CKD is growing worldwide, becoming a widely recognized problem for public health. The general increase in the average age of the Microorganisms 2021, 9, 1316. Microorganisms 2021, 9, 1316 population and the decrease in the mortality of patients at risk of renal failure are among the main factors linked to the increased incidence of CKD. Due to the increasing costs for the management of CKD and ESRD patients, researchers are searching for alternative strategies to treat CKD patients

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