Comprehensive and semi-quantitative analysis of carboxyl-containing metabolites related to gut microbiota on chronic kidney disease using 2-picolylamine isotopic labeling LC-MS/MS
Comprehensive and semi-quantitative analysis of carboxyl-containing metabolites related to gut microbiota on chronic kidney disease using 2-picolylamine isotopic labeling LC-MS/MS
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DOI：
10.1038/s41598-019-55600-1
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发表时间：
2019-12-13
影响因子：
4.6
通讯作者：
Mano, Nariyasu
中科院分区：
文献类型：
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作者：
Kanemitsu, Yoshitomi;Mishima, Eikan;Mano, Nariyasu
含羧基代谢物，如胆汁酸和脂肪酸，具有许多重要功能，微生物群参与它们的产生。在先前的研究中，我们发现在无菌条件下饲养的慢性肾脏病（CKD）模型小鼠比具有肠道微生物群的小鼠提供更严重的肾损伤。然而，微生物组和含羧基代谢物对肾功能的确切影响尚不清楚。在这项研究中，我们的目的是开发一种新的化学同位素标记-LC-MS/MS方法使用2-吡啶甲基胺及其同位素体，并应用于微生物组和CKD病理生理学的影响分析。所建立的半定量方法具有不亚于绝对定量的高准确度。通过比较四组小鼠，我们发现微生物群和肾功能都可以改变血浆和肠道中这些代谢物的组成和水平。特别是，吲哚-3-乙酸，短链脂肪酸和n-3型多不饱和脂肪酸，发挥重要作用的内皮屏障功能，肠道水平显着降低无菌条件下的肾功能衰竭小鼠。因此，这表明这些代谢物可能通过抑制上皮屏障破坏对CKD具有肾保护作用。
Carboxyl-containing metabolites, such as bile acids and fatty acids, have many important functions and microbiota is involved in the production of them. In the previous study, we found that the chronic kidney disease (CKD) model mice raised under germ-free conditions provided more severe renal damage than the mice with commensal microbiota. However, the precise influence by the microbiome and carboxyl-containing metabolites to the renal functions is unknown. In this study, we aimed to develop a novel chemical isotope labeling-LC-MS/MS method using the 2-picolylamine and its isotopologue and applied the analysis of effects of microbiome and CKD pathophysiology. The developed semi-quantitative method provided the high accuracy not inferior to the absolute quantification. By comparing of four groups of mice, we found that both microbiota and renal function can alter the composition and level of these metabolites in both plasma and intestine. In particular, the intestinal level of indole-3-acetic acid, short-chain fatty acids and n-3 type of polyunsaturated fatty acid, which play important roles in the endothelial barrier function, were significantly lower in germ-free conditions mice with renal failure. Accordingly, it is suggested these metabolites might have a renoprotective effect on CKD by suppressing epithelial barrier disruption.