Integrated analysis of the faecal metagenome and serum metabolome reveals the role of gut microbiome-associated metabolites in the detection of colorectal cancer and adenoma.
Integrated analysis of the faecal metagenome and serum metabolome reveals the role of gut microbiome-associated metabolites in the detection of colorectal cancer and adenoma.
复制标题
粪便宏基因组和血清代谢组的综合分析揭示了肠道微生物组相关代谢物在结直肠癌和腺瘤检测中的作用。
DOI：
10.1136/gutjnl-2020-323476
复制
发表时间：
2022-07
期刊：
影响因子：
24.5
通讯作者：
Cui, Wei
中科院分区：
文献类型：
--
作者：
Chen, Feng;Dai, Xudong;Zhou, Chang-Chun;Li, Ke-Xin;Zhang, Yu-Juan;Lou, Xiao-Ying;Zhu, Yuan-Min;Sun, Yan-Lai;Peng, Bao-Xiang;Cui, Wei
分析血清中与肠道微生物组相关的代谢物，并研究这些代谢物是否能够区分结直肠癌（CRC）或腺瘤患者与正常健康个体。
采用液相色谱 - 质谱法对血清进行非靶向代谢组学分析以及对配对粪便样本进行宏基因组测序的综合分析，以鉴定在CRC和腺瘤患者中丰度显著改变的与肠道微生物组相关的代谢物。通过靶向代谢组学分析测试了这些代谢物区分CRC和结直肠腺瘤的能力。建立了一个基于与肠道微生物组相关代谢物的模型，并在一个独立的验证队列中进行了评估。
总共有885种血清代谢物在CRC和腺瘤中均发生显著改变，其中包括8种与肠道微生物组相关的血清代谢物（GMSM组合），这8种代谢物通过靶向和非靶向代谢组学分析均可重复检测到，并能准确区分CRC和腺瘤与正常样本。一个基于GMSM组合的预测CRC和结直肠腺瘤的模型在建模队列中曲线下面积（AUC）为0.98（95%置信区间为0.94 - 1.00），在验证队列中AUC为0.92（灵敏度为83.5%，特异性为84.9%）。在验证队列样本中，GMSM模型明显优于临床标志物癌胚抗原（AUC为0.92对0.72），并且对腺瘤（AUC = 0.84）和早期CRC（AUC = 0.93）也显示出有前景的诊断准确性。
CRC患者的肠道微生物组重编程与血清代谢组的改变有关，GMSM在CRC和腺瘤检测方面具有潜在应用价值。
To profile gut microbiome-associated metabolites in serum and investigate whether these metabolites could distinguish individuals with colorectal cancer (CRC) or adenoma from normal healthy individuals. Integrated analysis of untargeted serum metabolomics by liquid chromatography-mass spectrometry and metagenome sequencing of paired faecal samples was applied to identify gut microbiome-associated metabolites with significantly altered abundance in patients with CRC and adenoma. The ability of these metabolites to discriminate between CRC and colorectal adenoma was tested by targeted metabolomic analysis. A model based on gut microbiome-associated metabolites was established and evaluated in an independent validation cohort. In total, 885 serum metabolites were significantly altered in both CRC and adenoma, including eight gut microbiome-associated serum metabolites (GMSM panel) that were reproducibly detected by both targeted and untargeted metabolomics analysis and accurately discriminated CRC and adenoma from normal samples. A GMSM panel-based model to predict CRC and colorectal adenoma yielded an area under the curve (AUC) of 0.98 (95% CI 0.94 to 1.00) in the modelling cohort and an AUC of 0.92 (83.5% sensitivity, 84.9% specificity) in the validation cohort. The GMSM model was significantly superior to the clinical marker carcinoembryonic antigen among samples within the validation cohort (AUC 0.92 vs 0.72) and also showed promising diagnostic accuracy for adenomas (AUC=0.84) and early-stage CRC (AUC=0.93). Gut microbiome reprogramming in patients with CRC is associated with alterations of the serum metabolome, and GMSMs have potential applications for CRC and adenoma detection.
登录
查看更多内容
影响因子：
24.5
作者：
Doubeni CA;Corley DA;Quinn VP;Jensen CD;Zauber AG;Goodman M;Johnson JR;Mehta SJ;Becerra TA;Zhao WK;Schottinger J;Doria-Rose VP;Levin TR;Weiss NS;Fletcher RH
通讯作者：
Fletcher RH
影响因子：
64.8
作者：
Devkota, Suzanne;Wang, Yunwei;Musch, Mark W.;Leone, Vanessa;Fehlner-Peach, Hannah;Nadimpalli, Anuradha;Antonopoulos, Dionysios A.;Jabri, Bana;Chang, Eugene B.
通讯作者：
Chang, Eugene B.
影响因子：
3.7
作者：
Nishiumi S;Kobayashi T;Ikeda A;Yoshie T;Kibi M;Izumi Y;Okuno T;Hayashi N;Kawano S;Takenawa T;Azuma T;Yoshida M
通讯作者：
Yoshida M
影响因子：
2.2
作者：
Huber, Charlotte A.;Pfluger, Valentin;Paterson, David L.
通讯作者：
Paterson, David L.
影响因子：
6.4
作者：
Koh, Gar Yee;Kane, Anne;Crott, Jimmy W.
通讯作者：
Crott, Jimmy W.