Abstract

Background: Chronic kidney disease (CKD) is a renal disorder characterized by the accumulation of uremic toxins with limited strategies to reduce their concentrations. A large amount of data supports the pivotal role of intestinal microbiota in CKD complications and as a major source of uremic toxins production. Here, we explored whether fecal microbiota transplantation (FMT) could be attenuated in metabolic complication and uremic toxin accumulation in mice with CKD. Methods: Kidney failure was chemically induced by a diet containing 0.25% (w/w) of adenine for four weeks. Mice were randomized into three groups: control, CKD and CKD + FMT groups. After four weeks, CKD mice underwent fecal microbiota transplantation (FMT) from healthy mice or phosphate buffered saline as control. The gut microbiota structure, uremic toxins plasmatic concentrations, and metabolic profiles were explored three weeks after transplantation. Results: Associated with the increase of alpha diversity, we observed a noticeable improvement of gut microbiota disturbance, after FMT treatment. FMT further decreased p-cresyl sulfate accumulation and improved glucose tolerance. There was no change in kidney function. Conclusions: These data indicate that FMT limited the accumulation of uremic toxins issued from intestinal cresol pathway by a beneficial effect on gut microbiota diversity. Further studies are needed to investigate the FMT efficiency, the timing and feces amount for the transplantation before, to become a therapeutic option in CKD patients.

Highlights

  • Kidney disease is one of the major health burdens worldwide, concerning approximately350 million people worldwide and resulting in a high mortality rate of 1 million deaths/year among patients in a state of advanced chronic kidney disease (CKD) and end stage kidney disease (ESKD) [1].Interestingly, in recent years, a growing body of data identified that dysbiosis in patients withCKD has been sculpting a detrimental metabolome, involved in detrimental clinical outcome [2].The progression of CKD to ESKD and its cardiovascular complications are related to uremic toxinsToxins 2020, 12, 741; doi:10.3390/toxins12120741 www.mdpi.com/journal/toxins (UTs) accumulation [3]

  • Body weight and food intake were significantly decreased in both CKD groups compared with the control group, but no change was observed between CKD and CKD+fecal microbiota transplantation (FMT). (Figure 2A,B)

  • We investigated the influence and effect of FMT on metabolic a profound taxonomic and functional imbalance that could be reversed with an FMT from healthy parameters, uremic toxin levels and fecal microbiota composition in CKD mice

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Summary

Introduction

Kidney disease is one of the major health burdens worldwide, concerning approximately350 million people worldwide and resulting in a high mortality rate of 1 million deaths/year among patients in a state of advanced chronic kidney disease (CKD) and end stage kidney disease (ESKD) [1].Interestingly, in recent years, a growing body of data identified that dysbiosis in patients withCKD has been sculpting a detrimental metabolome, involved in detrimental clinical outcome [2].The progression of CKD to ESKD and its cardiovascular complications are related to uremic toxinsToxins 2020, 12, 741; doi:10.3390/toxins12120741 www.mdpi.com/journal/toxins (UTs) accumulation [3]. 350 million people worldwide and resulting in a high mortality rate of 1 million deaths/year among patients in a state of advanced chronic kidney disease (CKD) and end stage kidney disease (ESKD) [1]. The progression of CKD to ESKD and its cardiovascular complications are related to uremic toxins. Up to date therapies for reducing production and levels of these UTs are missing but are needed to reduce morbi-mortality in patients with CKD [4,6,7]. Chronic kidney disease (CKD) is a renal disorder characterized by the accumulation of uremic toxins with limited strategies to reduce their concentrations. A large amount of data supports the pivotal role of intestinal microbiota in CKD complications and as a major source of uremic toxins production. Could be attenuated in metabolic complication and uremic toxin accumulation in mice with CKD

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