TY - JOUR
T1 - Gut-microbiota-metabolite axis in early renal function decline
AU - Barrios, Clara
AU - Beaumont, Michelle
AU - Pallister, Tess
AU - Villar, Judith
AU - Goodrich, Julia K
AU - Clark, Andrew
AU - Pascual, Julio
AU - Ley, Ruth E
AU - Spector, Tim D
AU - Bell, Jordana T
AU - Menni, Cristina
PY - 2015/8/4
Y1 - 2015/8/4
N2 - 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 = 8.8×10-29), p-cresyl-sulfate (-1.99(0.24), P = 4.6×10-16), and phenylacetylglutamine(-2.73 (0.25), P = 1.2×10-25) 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.
AB - 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 = 8.8×10-29), p-cresyl-sulfate (-1.99(0.24), P = 4.6×10-16), and phenylacetylglutamine(-2.73 (0.25), P = 1.2×10-25) 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.
UR - http://www.scopus.com/inward/record.url?scp=84942288138&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0134311
DO - 10.1371/journal.pone.0134311
M3 - Article
C2 - 26241311
AN - SCOPUS:84942288138
SN - 1932-6203
VL - 10
JO - PL o S One
JF - PL o S One
IS - 8
M1 - e0134311
ER -