Gut Microbiota and Their Derived Metabolites, a Search for Potential Targets to Limit Accumulation of Protein-Bound Uremic Toxins in Chronic Kidney Disease

Chronic kidney disease (CKD) is characterized by gut dysbiosis with a decrease in short-chain fatty acid (SCFA)-producing bacteria. Levels of protein-bound uremic toxins (PBUTs) and post-translational modifications (PTMs) of albumin increase with CKD, both risk factors for cardiovascular morbidity a...

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Autores principales:	Mieke Steenbeke, Sophie Valkenburg, Tessa Gryp, Wim Van Biesen, Joris R. Delanghe, Marijn M. Speeckaert, Griet Glorieux
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	chronic kidney disease uremic toxins short-chain fatty acids (SCFAs) albumin symmetry factor fecal samples Medicine R
Acceso en línea:	https://doaj.org/article/0537b022e8b3467bbb75822ecd4032c8
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spelling	oai:doaj.org-article:0537b022e8b3467bbb75822ecd4032c82021-11-25T19:09:00ZGut Microbiota and Their Derived Metabolites, a Search for Potential Targets to Limit Accumulation of Protein-Bound Uremic Toxins in Chronic Kidney Disease10.3390/toxins131108092072-6651https://doaj.org/article/0537b022e8b3467bbb75822ecd4032c82021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6651/13/11/809https://doaj.org/toc/2072-6651Chronic kidney disease (CKD) is characterized by gut dysbiosis with a decrease in short-chain fatty acid (SCFA)-producing bacteria. Levels of protein-bound uremic toxins (PBUTs) and post-translational modifications (PTMs) of albumin increase with CKD, both risk factors for cardiovascular morbidity and mortality. The relationship between fecal metabolites and plasma concentrations of PBUTs in different stages of CKD (<i>n</i> = 103) was explored. Estimated GFR tends to correlate with fecal butyric acid (BA) concentrations (<i>r<sub>s</sub></i> = 0.212; <i>p</i> = 0.032), which, in its turn, correlates with the abundance of SCFA-producing bacteria. Specific SCFAs correlate with concentrations of PBUT precursors in feces. Fecal levels of <i>p</i>-cresol correlate with its derived plasma UTs (<i>p</i>-cresyl sulfate: <i>r<sub>s</sub></i> = 0.342, <i>p</i> < 0.001; <i>p</i>-cresyl glucuronide: <i>r<sub>s</sub></i> = 0.268, <i>p</i> = 0.006), whereas an association was found between fecal and plasma levels of indole acetic acid (<i>r<sub>s</sub></i> = 0.306; <i>p</i> = 0.002). Finally, the albumin symmetry factor correlates positively with eGFR (<i>r<sub>s</sub></i> = 0.274; <i>p</i> = 0.005). The decreased abundance of SCFA-producing gut bacteria in parallel with the fecal concentration of BA and indole could compromise the intestinal barrier function in CKD. It is currently not known if this contributes to increased plasma levels of PBUTs, potentially playing a role in the PTMs of albumin. Further evaluation of SCFA-producing bacteria and SCFAs as potential targets to restore both gut dysbiosis and uremia is needed.Mieke SteenbekeSophie ValkenburgTessa GrypWim Van BiesenJoris R. DelangheMarijn M. SpeeckaertGriet GlorieuxMDPI AGarticlechronic kidney diseaseuremic toxinsshort-chain fatty acids (SCFAs)albumin symmetry factorfecal samplesMedicineRENToxins, Vol 13, Iss 809, p 809 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	chronic kidney disease uremic toxins short-chain fatty acids (SCFAs) albumin symmetry factor fecal samples Medicine R
spellingShingle	chronic kidney disease uremic toxins short-chain fatty acids (SCFAs) albumin symmetry factor fecal samples Medicine R Mieke Steenbeke Sophie Valkenburg Tessa Gryp Wim Van Biesen Joris R. Delanghe Marijn M. Speeckaert Griet Glorieux Gut Microbiota and Their Derived Metabolites, a Search for Potential Targets to Limit Accumulation of Protein-Bound Uremic Toxins in Chronic Kidney Disease
description	Chronic kidney disease (CKD) is characterized by gut dysbiosis with a decrease in short-chain fatty acid (SCFA)-producing bacteria. Levels of protein-bound uremic toxins (PBUTs) and post-translational modifications (PTMs) of albumin increase with CKD, both risk factors for cardiovascular morbidity and mortality. The relationship between fecal metabolites and plasma concentrations of PBUTs in different stages of CKD (<i>n</i> = 103) was explored. Estimated GFR tends to correlate with fecal butyric acid (BA) concentrations (<i>r<sub>s</sub></i> = 0.212; <i>p</i> = 0.032), which, in its turn, correlates with the abundance of SCFA-producing bacteria. Specific SCFAs correlate with concentrations of PBUT precursors in feces. Fecal levels of <i>p</i>-cresol correlate with its derived plasma UTs (<i>p</i>-cresyl sulfate: <i>r<sub>s</sub></i> = 0.342, <i>p</i> < 0.001; <i>p</i>-cresyl glucuronide: <i>r<sub>s</sub></i> = 0.268, <i>p</i> = 0.006), whereas an association was found between fecal and plasma levels of indole acetic acid (<i>r<sub>s</sub></i> = 0.306; <i>p</i> = 0.002). Finally, the albumin symmetry factor correlates positively with eGFR (<i>r<sub>s</sub></i> = 0.274; <i>p</i> = 0.005). The decreased abundance of SCFA-producing gut bacteria in parallel with the fecal concentration of BA and indole could compromise the intestinal barrier function in CKD. It is currently not known if this contributes to increased plasma levels of PBUTs, potentially playing a role in the PTMs of albumin. Further evaluation of SCFA-producing bacteria and SCFAs as potential targets to restore both gut dysbiosis and uremia is needed.
format	article
author	Mieke Steenbeke Sophie Valkenburg Tessa Gryp Wim Van Biesen Joris R. Delanghe Marijn M. Speeckaert Griet Glorieux
author_facet	Mieke Steenbeke Sophie Valkenburg Tessa Gryp Wim Van Biesen Joris R. Delanghe Marijn M. Speeckaert Griet Glorieux
author_sort	Mieke Steenbeke
title	Gut Microbiota and Their Derived Metabolites, a Search for Potential Targets to Limit Accumulation of Protein-Bound Uremic Toxins in Chronic Kidney Disease
title_short	Gut Microbiota and Their Derived Metabolites, a Search for Potential Targets to Limit Accumulation of Protein-Bound Uremic Toxins in Chronic Kidney Disease
title_full	Gut Microbiota and Their Derived Metabolites, a Search for Potential Targets to Limit Accumulation of Protein-Bound Uremic Toxins in Chronic Kidney Disease
title_fullStr	Gut Microbiota and Their Derived Metabolites, a Search for Potential Targets to Limit Accumulation of Protein-Bound Uremic Toxins in Chronic Kidney Disease
title_full_unstemmed	Gut Microbiota and Their Derived Metabolites, a Search for Potential Targets to Limit Accumulation of Protein-Bound Uremic Toxins in Chronic Kidney Disease
title_sort	gut microbiota and their derived metabolites, a search for potential targets to limit accumulation of protein-bound uremic toxins in chronic kidney disease
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0537b022e8b3467bbb75822ecd4032c8
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Gut Microbiota and Their Derived Metabolites, a Search for Potential Targets to Limit Accumulation of Protein-Bound Uremic Toxins in Chronic Kidney Disease

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