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Gut-Microbiota-Metabolite Axis in Early Renal Function Decline
INTRODUCTION: Several circulating metabolites derived from bacterial protein fermentation have been found to be inversely associated with renal function but the timing and disease severity is unclear. The aim of this study is to explore the relationship between indoxyl-sulfate, p-cresyl-sulfate, phe...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4524635/ https://www.ncbi.nlm.nih.gov/pubmed/26241311 http://dx.doi.org/10.1371/journal.pone.0134311 |
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author | Barrios, Clara Beaumont, Michelle Pallister, Tess Villar, Judith Goodrich, Julia K. Clark, Andrew Pascual, Julio Ley, Ruth E. Spector, Tim D. Bell, Jordana T. Menni, Cristina |
author_facet | Barrios, Clara Beaumont, Michelle Pallister, Tess Villar, Judith Goodrich, Julia K. Clark, Andrew Pascual, Julio Ley, Ruth E. Spector, Tim D. Bell, Jordana T. Menni, Cristina |
author_sort | Barrios, Clara |
collection | PubMed |
description | INTRODUCTION: Several circulating metabolites derived from bacterial protein fermentation have been found to be inversely associated with renal function but the timing and disease severity is unclear. The aim of this study is to explore the relationship between indoxyl-sulfate, p-cresyl-sulfate, phenylacetylglutamine and gut-microbial profiles in early renal function decline. RESULTS: Indoxyl-sulfate (Beta(SE) = -2.74(0.24); P = 8.8x10(-29)), p-cresyl-sulfate (-1.99(0.24), P = 4.6x10(-16)), and phenylacetylglutamine(-2.73 (0.25), P = 1.2x10(-25)) were inversely associated with eGFR in a large population base cohort (TwinsUK, n = 4439) with minimal renal function decline. In a sub-sample of 855 individuals, we analysed metabolite associations with 16S gut microbiome profiles (909 profiles, QIIME 1.7.0). Three Operational Taxonomic Units (OTUs) were significantly associated with indoxyl-sulfate and 52 with phenylacetylglutamine after multiple testing; while one OTU was nominally associated with p-cresyl sulfate. All 56 microbial members belong to the order Clostridiales and are represented by anaerobic Gram-positive families Christensenellaceae, Ruminococcaceae and Lachnospiraceae. Within these, three microbes were also associated with eGFR. CONCLUSIONS: Our data suggest that indoxyl-sulfate, p-cresyl-sulfate and phenylacetylglutamine are early markers of renal function decline. Changes in the intestinal flora associated with these metabolites are detectable in early kidney disease. Future efforts should dissect this relationship to improve early diagnostics and therapeutics strategies. |
format | Online Article Text |
id | pubmed-4524635 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-45246352015-08-06 Gut-Microbiota-Metabolite Axis in Early Renal Function Decline Barrios, Clara Beaumont, Michelle Pallister, Tess Villar, Judith Goodrich, Julia K. Clark, Andrew Pascual, Julio Ley, Ruth E. Spector, Tim D. Bell, Jordana T. Menni, Cristina PLoS One Research Article INTRODUCTION: Several circulating metabolites derived from bacterial protein fermentation have been found to be inversely associated with renal function but the timing and disease severity is unclear. The aim of this study is to explore the relationship between indoxyl-sulfate, p-cresyl-sulfate, phenylacetylglutamine and gut-microbial profiles in early renal function decline. RESULTS: Indoxyl-sulfate (Beta(SE) = -2.74(0.24); P = 8.8x10(-29)), p-cresyl-sulfate (-1.99(0.24), P = 4.6x10(-16)), and phenylacetylglutamine(-2.73 (0.25), P = 1.2x10(-25)) were inversely associated with eGFR in a large population base cohort (TwinsUK, n = 4439) with minimal renal function decline. In a sub-sample of 855 individuals, we analysed metabolite associations with 16S gut microbiome profiles (909 profiles, QIIME 1.7.0). Three Operational Taxonomic Units (OTUs) were significantly associated with indoxyl-sulfate and 52 with phenylacetylglutamine after multiple testing; while one OTU was nominally associated with p-cresyl sulfate. All 56 microbial members belong to the order Clostridiales and are represented by anaerobic Gram-positive families Christensenellaceae, Ruminococcaceae and Lachnospiraceae. Within these, three microbes were also associated with eGFR. CONCLUSIONS: Our data suggest that indoxyl-sulfate, p-cresyl-sulfate and phenylacetylglutamine are early markers of renal function decline. Changes in the intestinal flora associated with these metabolites are detectable in early kidney disease. Future efforts should dissect this relationship to improve early diagnostics and therapeutics strategies. Public Library of Science 2015-08-04 /pmc/articles/PMC4524635/ /pubmed/26241311 http://dx.doi.org/10.1371/journal.pone.0134311 Text en © 2015 Barrios et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Barrios, Clara Beaumont, Michelle Pallister, Tess Villar, Judith Goodrich, Julia K. Clark, Andrew Pascual, Julio Ley, Ruth E. Spector, Tim D. Bell, Jordana T. Menni, Cristina Gut-Microbiota-Metabolite Axis in Early Renal Function Decline |
title | Gut-Microbiota-Metabolite Axis in Early Renal Function Decline |
title_full | Gut-Microbiota-Metabolite Axis in Early Renal Function Decline |
title_fullStr | Gut-Microbiota-Metabolite Axis in Early Renal Function Decline |
title_full_unstemmed | Gut-Microbiota-Metabolite Axis in Early Renal Function Decline |
title_short | Gut-Microbiota-Metabolite Axis in Early Renal Function Decline |
title_sort | gut-microbiota-metabolite axis in early renal function decline |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4524635/ https://www.ncbi.nlm.nih.gov/pubmed/26241311 http://dx.doi.org/10.1371/journal.pone.0134311 |
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