School of Life Science and Technology, Tokyo Institute of Technology, Tokyo, Japan.
Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan.
mSystems. 2022 Apr 26;7(2):e0001822. doi: 10.1128/msystems.00018-22. Epub 2022 Mar 21.
Accumulating evidence indicates that the gut microbiome and metabolites are associated with colorectal cancer (CRC). However, the influence of surgery for CRC treatment on the gut microbiome and metabolites and how it relates to CRC risk in postoperative CRC patients remain partially understood. Here, we collected 170 fecal samples from 85 CRC patients pre- and approximately 1 year postsurgery and performed shotgun metagenomic sequencing and capillary electrophoresis-time of flight mass spectrometry-based metabolomics analyses to characterize alterations between pre- and postsurgery. We determined that the relative abundance of 114 species was altered postsurgery (0.005). CRC-associated species, such as Fusobacterium nucleatum, were decreased postsurgery. On the other hand, Clostridium scindens, carcinogenesis-associated deoxycholate (DCA)-producing species, and its biotransformed genes ( operon) were increased postsurgery. The concentration of 60 fecal metabolites was also altered postsurgery (0.005). Two bile acids, cholate and DCA, were increased postsurgery. We developed methods to estimate postoperative CRC risk based on the gut microbiome and metabolomic compositions using a random forest machine-learning algorithm that classifies large adenoma or early-stage CRC and healthy controls from publicly available data sets. We applied methods to preoperative samples and then compared the estimated CRC risk between the two groups according to the presence of large adenoma or tumors 5 years postsurgery (0.05). Overall, our results show that the gut microbiome and metabolites dynamically change from pre- to postsurgery. In postoperative CRC patients, potential CRC risk derived from gut microbiome and metabolites still remains, which indicates the importance of follow-up assessments. The gut microbiome and metabolites are associated with CRC progression and carcinogenesis. Postoperative CRC patients are reported to be at an increased CRC risk; however, how gut microbiome and metabolites are related to CRC risk in postoperative patients remains only partially understood. In this study, we investigated the influence of surgical CRC treatment on the gut microbiome and metabolites. We found that the CRC-associated species Fusobacterium nucleatum was decreased postsurgery, whereas carcinogenesis-associated DCA and its producing species and genes were increased postsurgery. We developed methods to estimate postoperative CRC risk based on the gut microbiome and metabolomic compositions. We applied methods to compare the estimated CRC risk between two groups according to the presence of large adenoma or tumors after 5 years postsurgery. To our knowledge, this study is the first report on differences between pre- and postsurgery using metagenomics and metabolomics data analysis. Our methods might be used for CRC risk assessment in postoperative patients.
越来越多的证据表明，肠道微生物组和代谢物与结直肠癌（CRC）有关。然而，CRC 治疗手术对肠道微生物组和代谢物的影响，以及它与术后 CRC 患者的 CRC 风险有何关联，仍部分未知。在这里，我们收集了 85 名 CRC 患者术前和术后约 1 年的 170 份粪便样本，并进行了 shotgun 宏基因组测序和毛细管电泳-飞行时间质谱代谢组学分析，以描述术前和术后的变化。我们发现，114 种物种的相对丰度在术后发生了改变（0.005）。CRC 相关物种，如具核梭杆菌，在术后减少。另一方面，结瘤相关的脱氧胆酸（DCA）产生菌梭状芽胞杆菌和其生物转化基因（操纵子）在术后增加。60 种粪便代谢物的浓度也在术后发生了改变（0.005）。两种胆酸，胆酸和 DCA，在术后增加。我们使用随机森林机器学习算法开发了基于肠道微生物组和代谢组组成的术后 CRC 风险估计方法，该算法可以从公开的数据集区分大腺瘤或早期 CRC 和健康对照。我们将方法应用于术前样本，然后根据 5 年后是否存在大腺瘤或肿瘤比较两组之间的估计 CRC 风险（0.05）。总的来说，我们的结果表明，肠道微生物组和代谢物从术前到术后动态变化。在术后 CRC 患者中，源自肠道微生物组和代谢物的潜在 CRC 风险仍然存在，这表明需要进行随访评估。肠道微生物组和代谢物与 CRC 的进展和癌变有关。据报道，术后 CRC 患者的 CRC 风险增加；然而，肠道微生物组和代谢物与术后患者 CRC 风险的关系仍知之甚少。在这项研究中，我们调查了 CRC 治疗手术对肠道微生物组和代谢物的影响。我们发现，与 CRC 相关的物种具核梭杆菌在术后减少，而与癌变相关的 DCA 及其产生菌和基因在术后增加。我们开发了基于肠道微生物组和代谢组组成的术后 CRC 风险估计方法。我们应用方法根据 5 年后是否存在大腺瘤或肿瘤比较两组之间的估计 CRC 风险。据我们所知，这是首次使用宏基因组学和代谢组学数据分析报告术前和术后的差异。我们的方法可用于术后患者的 CRC 风险评估。
