Vincent Coates Foundation Mass Spectrometry Laboratory, Stanford University, Stanford, California, USA.
J Am Soc Nephrol. 2011 Sep;22(9):1769-76. doi: 10.1681/ASN.2010121220. Epub 2011 Jul 22.
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: α-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.
结肠中的微生物会产生化合物,这些化合物通常会被肾脏排出,它们是潜在的尿毒症毒素。虽然对邻苯二酚硫酸盐和吲哚硫酸酯已有深入研究,但人们对其他化合物知之甚少。在这里,我们比较了有结肠和无结肠的血液透析患者的血浆,以鉴定和进一步描述源自结肠的尿毒症溶质。HPLC 证实了邻苯二酚硫酸盐和吲哚硫酸酯的结肠来源,但无结肠患者的马尿酸、甲胺和二甲胺水平并没有显著降低。高分辨率质谱检测到预透析血浆样本中存在 1000 多种特征。基于这些特征的层次聚类清楚地将有结肠和无结肠的透析患者区分开来。与有结肠的患者相比,我们在无结肠的患者中发现了 30 多种特征,这些特征要么不存在,要么存在浓度较低。几乎所有这些特征在无结肠的透析患者中比在正常受试者中更为突出,这表明它们代表尿毒症溶质。我们使用一组吲哚和苯标准品来鉴定五种源自结肠的尿毒症溶质:α-苯乙酰基-l-谷氨酰胺、5-羟基吲哚、吲哚基葡萄糖醛酸、邻苯二酚硫酸盐和吲哚硫酸酯。然而,在标准代谢组学数据库中无法找到与大多数源自结肠的溶质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大量尿毒症溶质,其中大多数仍未被识别。