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, hen...

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Autores: Barrios Barrera, Clara, Beaumont, Michelle, Pallister, Tess, Villar García, Judit, Goodrich, Julia K., Clark, Andrew, Pascual Santos, Julio, Ley, Ruth E., Spector, Tim D., Bell, Jordana T., Menni, Cristina
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2015
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/24802
Acceso en línea:http://hdl.handle.net/10230/24802
http://dx.doi.org/10.1371/journal.pone.0134311
Access Level:acceso abierto
Palabra clave:Aparell urinari -- Fisiologia
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spelling Gut-Microbiota-Metabolite Axis in Early Renal Function Decline.Barrios Barrera, ClaraBeaumont, MichellePallister, TessVillar García, JuditGoodrich, Julia K.Clark, AndrewPascual Santos, JulioLey, Ruth E.Spector, Tim D.Bell, Jordana T.Menni, CristinaAparell urinari -- FisiologiaINTRODUCTION: 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, henylacetylglutamine 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.TwinsUK was funded by the Wellcome Trust; European Community’s Seventh Framework Programme (FP7/2007-2013). The study also receives support from the National Institute for Health Research (NIHR) Clinical Research Facility at Guy’s & St Thomas’ NHS Foundation Trust and NIHR Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust, the King's College London, the Cornell Centre for Comparative Population Genomics. Tim Spector is the holder of an ERC Advanced Principal Investigator award. Clara Barrios is supported by a grant from the Spanish Society of NephrologyPublic Library of Science201520152015info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/24802http://dx.doi.org/10.1371/journal.pone.0134311reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésPLoS One. 2015 Aug 4;10(8):e0134311: © 2015 Barrios et al. This is an open access article distributed under the terms of thehttp://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are/ncreditedhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/248022026-05-29T05:05:01Z
dc.title.none.fl_str_mv Gut-Microbiota-Metabolite Axis in Early Renal Function Decline.
title Gut-Microbiota-Metabolite Axis in Early Renal Function Decline.
spellingShingle Gut-Microbiota-Metabolite Axis in Early Renal Function Decline.
Barrios Barrera, Clara
Aparell urinari -- Fisiologia
title_short 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_sort Gut-Microbiota-Metabolite Axis in Early Renal Function Decline.
dc.creator.none.fl_str_mv Barrios Barrera, Clara
Beaumont, Michelle
Pallister, Tess
Villar García, Judit
Goodrich, Julia K.
Clark, Andrew
Pascual Santos, Julio
Ley, Ruth E.
Spector, Tim D.
Bell, Jordana T.
Menni, Cristina
author Barrios Barrera, Clara
author_facet Barrios Barrera, Clara
Beaumont, Michelle
Pallister, Tess
Villar García, Judit
Goodrich, Julia K.
Clark, Andrew
Pascual Santos, Julio
Ley, Ruth E.
Spector, Tim D.
Bell, Jordana T.
Menni, Cristina
author_role author
author2 Beaumont, Michelle
Pallister, Tess
Villar García, Judit
Goodrich, Julia K.
Clark, Andrew
Pascual Santos, Julio
Ley, Ruth E.
Spector, Tim D.
Bell, Jordana T.
Menni, Cristina
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Aparell urinari -- Fisiologia
topic Aparell urinari -- Fisiologia
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, henylacetylglutamine 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.
publishDate 2015
dc.date.none.fl_str_mv 2015
2015
2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/24802
http://dx.doi.org/10.1371/journal.pone.0134311
url http://hdl.handle.net/10230/24802
http://dx.doi.org/10.1371/journal.pone.0134311
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv PLoS One. 2015 Aug 4;10(8):e0134311
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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