Colonic Contribution to Uremic Solutes
Colonic Contribution to Uremic Solutes
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DOI：
10.1681/asn.2010121220
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发表时间：
2011-09-01
影响因子：
13.6
通讯作者：
Meyer, Timothy W.
中科院分区：
文献类型：
--
作者：
Aronov, Pavel A.;Luo, Frank J. -G.;Meyer, Timothy W.
结肠中的微生物产生化合物，通常由肾脏排出，这些化合物是潜在的尿毒症毒素。虽然硫酸对甲酚和硫酸吲哚酚是研究得很好的例子，但很少有其他化合物是已知的。在这里，我们比较了血液透析患者的血浆与不结肠，以确定和进一步表征结肠来源的尿毒症溶质。HPLC证实了对甲酚硫酸盐和硫酸吲哚酚的结肠来源，但马尿酸盐，甲胺和二甲胺的水平在没有结肠的患者中并没有显着降低。高分辨率质谱检测透析前血浆样本中的1000多个特征。基于这些特征的层次聚类清楚地区分了有结肠和无结肠的透析患者。与有结肠的患者相比，我们在没有结肠的患者中确定了30多个个体特征，这些特征要么不存在，要么以较低的浓度存在。几乎所有这些特征在透析患者血浆中比正常受试者更突出，表明它们代表尿毒症溶质。我们使用一组吲哚和苯基标准品来鉴定五种结肠来源的尿毒症溶质：a-苯乙酰基-L-谷氨酰胺、5-羟基吲哚、吲哚基葡糖苷酸、对甲酚硫酸盐和吲哚基硫酸盐。然而，在标准代谢组学数据库中找不到与大多数结肠衍生溶质匹配的具有准确质量值的化合物。这些结果表明，结肠微生物可能会产生一个重要部分的尿毒症溶质，其中大部分仍然不明。
Microbes in the colon produce compounds, normally excreted by the kidneys, which are potential uremic toxins. Although p-cresol sulfate and indoxyl sulfate are well studied examples, few other compounds are known. Here, we compared plasma from hemodialysis patients with and without colons to identify and further characterize colon-derived uremic solutes. HPLC confirmed the colonic origin of p-cresol sulfate and indoxyl sulfate, but levels of hippurate, methylamine, and dimethylamine were not significantly lower in patients without colons. High-resolution mass spectrometry detected more than 1000 features in predialysis plasma samples. Hierarchical clustering based on these features clearly separated dialysis patients with and without colons. Compared with patients with colons, we identified more than 30 individual features in patients without colons that were either absent or present in lower concentration. Almost all of these features were more prominent in plasma from dialysis patients than normal subjects, suggesting that they represented uremic solutes. We used a panel of indole and phenyl standards to identify five colon-derived uremic solutes: a-phenylacetyl-l-glutamine, 5-hydroxyindole, indoxyl glucuronide, p-cresol sulfate, and indoxyl sulfate. However, compounds with accurate mass values matching most of the colon-derived solutes could not be found in standard metabolomic databases. These results suggest that colonic microbes may produce an important portion of uremic solutes, most of which remain unidentified.