Gut-Microbiota-Metabolite Axis in Early Renal Function Decline.
Gut-Microbiota-Metabolite Axis in Early Renal Function Decline.
复制标题
DOI：
10.1371/journal.pone.0134311
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Menni C
中科院分区：
文献类型：
--
作者：
Barrios C;Beaumont M;Pallister T;Villar J;Goodrich JK;Clark A;Pascual J;Ley RE;Spector TD;Bell JT;Menni C
已发现来自细菌蛋白发酵的几种循环代谢物与肾功能呈负相关，但时间和疾病严重程度尚不清楚。本研究旨在探讨硫酸吲哚酚、对甲苯基硫酸酯、苯乙酰谷氨酰胺与早期肾功能下降肠道微生物谱的关系。硫酸吲哚酚（β（SE）= -2.74（0.24）; P = 8.8x10-29），对甲苯基硫酸盐（-1.99（0.24），P = 4.6x10-16）和苯乙酰谷氨酰胺（-2.73（0.25），P = 1.2x10-25）与eGFR呈负相关（TwinsUK，n = 4439），肾功能下降最小。在855名个体的子样本中，我们分析了代谢物与16 S肠道微生物组特征的相关性（909个特征，QIIME 1.7.0）。在多次测试后，三个操作分类单位（OTU）与硫酸吲哚酚显著相关，52个与苯乙酰谷氨酰胺显著相关;而一个OTU名义上与硫酸对甲苯酯相关。所有56个微生物成员都属于梭菌目，并以厌氧革兰氏阳性家族Christensenellaceae、Ruminococcaceae和Lachnospiraceae为代表。其中，三种微生物也与eGFR相关。我们的数据表明，硫酸吲哚酚、对甲苯基硫酸酯和苯乙酰谷氨酰胺是肾功能下降的早期标志物。与这些代谢物相关的肠道植物群的变化在早期肾脏疾病中可检测到。未来的努力应该剖析这种关系，以改善早期诊断和治疗策略。
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. 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. 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.