Gut Microbiome Profiling Uncovers a Lower Abundance of Butyricicoccus in Advanced Stages of Chronic Kidney Disease.

Tessa Gryp,Marijn Speeckaert,Francis Verbeke,Wim Van Biesen,Griet Glorieux,Marie Joossens,Karoline Faust,Geert R. B. Huys,Mario Vaneechoutte,Jeroen Raes

doi:10.3390/jpm11111118

Abstract

Chronic kidney disease (CKD) is characterized by the accumulation of uremic toxins which exert deleterious effects on various organ systems. Several of these uremic toxins originate from the bacterial metabolization of aromatic amino acids in the colon. This study assessed whether the gut microbial composition varies among patients in different stages of CKD. Uremic metabolites were quantified by UPLC/fluorescence detection and microbial profiling by 16S rRNA amplicon sequencing. Gut microbial profiles of CKD patients were compared among stages 1–2, stage 3 and stages 4–5. Although a substantial inter-individual difference in abundance of the top 15 genera was observed, no significant difference was observed between groups. Bristol stool scale (BSS) correlated negatively with p-cresyl sulfate and hippuric acid levels, irrespective of the intake of laxatives. Butyricicoccus, a genus with butyrate-generating properties, was decreased in abundance in advanced stages of CKD compared to the earlier stages (p = 0.043). In conclusion, in this cross-sectional study no gradual differences in the gut microbial profile over the different stages of CKD were observed. However, the decrease in the abundance of Butyricicoccus genus with loss of kidney function stresses the need for more in-depth functional exploration of the gut microbiome in CKD patients not on dialysis.

Highlights

In chronic kidney disease (CKD), uremic toxins accumulate in the blood circulation [1,2,3], exerting deleterious effects on various organ systems of the human body [4]and contributing to cardiovascular morbidity and mortality [5,6,7,8,9]
The gut microbiota is responsible for the generation of the precursor metabolites of the protein-bound uremic toxins (PBUTs) such as p-cresyl sulfate, p-cresyl glucuronide, indoxyl sulfate (IxS) and indole-3-acetic acid (IAA)
The ‘Chronic kidney disease epidemiology collaboration (CKD-EPI)’-creatinine equation was used to determine the estimated glomerular filtration rate of each patient. Based on their eGFR, the total group of patients with CKD was divided into three groups: (i) eGFR above 60 mL/min/1.73 m2 corresponding to CKD stages 1 and 2 (n = 36), (ii) eGFR between 30 and 60 mL/min/1.73 m2 corresponding to CKD stage 3 (n = 44), and (iii) eGFR below 30 mL/min/1.73 m2 corresponding to CKD stages 4 and 5 (n = 31)

Summary

Introduction

In chronic kidney disease (CKD), uremic toxins accumulate in the blood circulation [1,2,3], exerting deleterious effects on various organ systems of the human body [4]and contributing to cardiovascular morbidity and mortality [5,6,7,8,9]. In chronic kidney disease (CKD), uremic toxins accumulate in the blood circulation [1,2,3], exerting deleterious effects on various organ systems of the human body [4]. The gut microbiota is responsible for the generation of the precursor metabolites of the protein-bound uremic toxins (PBUTs) such as p-cresyl sulfate (pCS), p-cresyl glucuronide (pCG), indoxyl sulfate (IxS) and indole-3-acetic acid (IAA). P-cresol and indole are detoxified through sulfation and glucuronidation by the colon mucosa and liver into pCS, pCG and IxS [15,16], whereas IAA enters the blood circulation unmodified [17,18]. Since only the free fraction can be removed by dialysis therapy [20,21], albumin-binding hampers their removal at end-stage kidney disease (ESKD)

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Conclusion