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Integrated study of metabolomics and gut metabolic activity from ulcerative colitis to colorectal cancer: The combined action of disordered gut microbiota and linoleic acid metabolic pathway might fuel cancer.
Journal of Chromatography A ( IF 4.1 ) Pub Date : 2020-08-20 , DOI: 10.1016/j.chroma.2020.461503
Qi Tang 1 , Song Cang 1 , Jiao Jiao 1 , Weiwei Rong 1 , Huarong Xu 1 , Kaishun Bi 1 , Qing Li 1 , Ran Liu 1
Affiliation  

Colorectal cancer (CRC) is one of the most serious complications of ulcerative colitis (UC). Altered gut microbiota is implicated in the development of CRC and metabolic perturbations are often associated with changes in the gut microbiome composition. Given the links between gut microbiome and the metabolic profiles in the body, an approach involving ultra-high-performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS) metabolomics and 16S rDNA sequencing technology was applied to trace the development UC into CRC in rats. The study identified 11 differential metabolites related to both UC and CRC, which mainly referred to the linoleic acid metabolism. Among these, linoleic acid and 12‑hydroxy‑8,10-octadecadienoic acid could serve as key biomarkers for the development of UC into CRC. Besides, a significant change was observed in the microflora structure during the development from UC to CRC; this mainly involved a gradual increase in Escherichia-Shigella and a gradual decrease in Lactobacillus. In addition, Pearson's correlation analysis revealed strong correlations between intestinal microflora-related metabolites and specific intestinal microflora, which indicated both of them can promote the transition of UC to CRC. The results of the present study provided positive support for the involvement of intestinal microflora and host metabolism in the pathophysiological mechanism that is responsible for the development of UC into CRC. This information can help understand the risk for CRC that accompanies a diagnosis of UC and also provide different means of targeting these differential metabolites and intestinal microbiota to avoid UC-induced CRC.



中文翻译:

从溃疡性结肠炎到结直肠癌的代谢组学和肠道代谢活性的综合研究:肠道菌群失调和亚油酸代谢途径的联合作用可能助长癌症。

大肠癌(CRC)是溃疡性结肠炎(UC)最严重的并发症之一。肠道微生物群的改变与CRC的发生有关,并且代谢紊乱通常与肠道微生物组组成的变化有关。考虑到肠道微生物组与体内代谢状况之间的联系,采用超高效液相色谱结合电喷雾电离四极杆飞行时间串联质谱(UHPLC-Q-TOF-MS / MS)代谢组学和方法应用16S rDNA测序技术将大鼠的发育UC追溯到CRC中。该研究确定了11种与UC和CRC相关的代谢产物,主要涉及亚油酸代谢。其中,亚油酸和12-羟基-8 10-十八碳二烯酸可以作为UC转化为CRC的关键生物标志物。此外,从UC到CRC的发育过程中,菌群结构发生了显着变化。这主要涉及逐步增加大肠杆菌,痢疾杆菌,并在逐渐减少乳酸杆菌。此外,Pearson的相关性分析显示肠道菌群相关代谢产物与特定肠道菌群之间存在强相关性,这表明它们都可以促进UC向CRC的转化。本研究的结果为肠道菌群和宿主代谢参与导致UC转化为CRC的病理生理机制提供了积极的支持。这些信息可以帮助了解伴随UC诊断的CRC风险,还可以提供针对这些差异代谢物和肠道菌群的不同方法,从而避免UC引起的CRC。

更新日期:2020-08-25
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