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Gut-Microbiota-Metabolite Axis in Early Renal Function Decline.

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dc.contributor.author Barrios Barrera, Clara
dc.contributor.author Beaumont, Michelle
dc.contributor.author Pallister, Tess
dc.contributor.author Villar García, Judit
dc.contributor.author Goodrich, Julia K.
dc.contributor.author Clark, Andrew
dc.contributor.author Pascual Santos, Julio
dc.contributor.author Ley, Ruth E.
dc.contributor.author Spector, Tim D.
dc.contributor.author Bell, Jordana T.
dc.contributor.author Menni, Cristina
dc.date.accessioned 2015-10-05T07:52:29Z
dc.date.available 2015-10-05T07:52:29Z
dc.date.issued 2015
dc.identifier.citation Barrios C, Beaumont M, Pallister T, Villar J, Goodrich JK, Clark A. et al. Gut-Microbiota-Metabolite Axis in Early Renal Function Decline. PLoS One. 2015 Aug 4;10(8):e0134311. doi: 10.1371/journal.pone.0134311.
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10230/24802
dc.description.abstract 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.
dc.description.sponsorship 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 Nephrology
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Public Library of Science
dc.relation.ispartof PLoS One. 2015 Aug 4;10(8):e0134311
dc.rights : © 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/ncredited
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.subject.other Aparell urinari -- Fisiologia
dc.title Gut-Microbiota-Metabolite Axis in Early Renal Function Decline.
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0134311
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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