Surgical Treatment for Colorectal Cancer Partially Restores Gut Microbiome and Metabolome Traits.
Surgical Treatment for Colorectal Cancer Partially Restores Gut Microbiome and Metabolome Traits.
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DOI：
10.1128/msystems.00018-22
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发表时间：
2022-04-26
期刊：
影响因子：
6.4
通讯作者：
中科院分区：
文献类型：
--
作者：
越来越多的证据表明，肠道微生物群和代谢物与结直肠癌（CRC）有关。然而，结直肠癌手术治疗对肠道微生物组和代谢物的影响及其与结直肠癌术后患者结直肠癌风险的关系仍部分了解。在这里，我们收集了85名结直肠癌患者手术前和术后约1年的170份粪便样本，并进行了鸟枪宏基因组测序和基于毛细管电泳-飞行时间质谱的代谢组学分析，以表征手术前后的变化。我们确定114种的相对丰度在手术后发生了改变（P < 0.005）。crc相关物种，如核梭杆菌，术后减少。另一方面，Clostridium scindens，致癌相关脱氧胆酸（DCA）产生菌及其生物转化基因（bai操纵子）在术后增加。60种粪便代谢物的浓度在术后也有改变（P < 0.005）。两种胆汁酸，胆酸和DCA，术后升高。我们开发了基于肠道微生物组和代谢组组成估计术后CRC风险的方法，使用随机森林机器学习算法，从公开可用的数据集中对大腺瘤或早期CRC和健康对照进行分类。我们将方法应用于术前样本，然后根据术后5年是否存在大腺瘤或肿瘤比较两组估计的CRC风险（P < 0.05）。总的来说，我们的研究结果表明，肠道微生物组和代谢物在手术前后发生了动态变化。在结直肠癌术后患者中，肠道微生物组和代谢物的潜在结直肠癌风险仍然存在，这表明随访评估的重要性。肠道微生物群和代谢物与结直肠癌的进展和癌变有关。据报道，术后结直肠癌患者发生结直肠癌的风险增加；然而，肠道微生物群和代谢物如何与术后患者结直肠癌风险相关仍然只是部分了解。在这项研究中，我们研究了手术治疗结直肠癌对肠道微生物组和代谢物的影响。我们发现crc相关物种核梭杆菌在手术后减少，而致癌相关的DCA及其产生物种和基因在手术后增加。我们开发了基于肠道微生物组和代谢组组成来评估术后结直肠癌风险的方法。我们采用方法比较两组患者术后5年是否存在较大腺瘤或肿瘤的CRC风险。据我们所知，这项研究是第一个使用宏基因组学和代谢组学数据分析手术前后差异的报告。我们的方法可用于术后患者CRC风险评估。
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 (P < 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 (bai operon) were increased postsurgery. The concentration of 60 fecal metabolites was also altered postsurgery (P < 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 (P < 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. IMPORTANCE 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.
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影响因子：
6.2
作者：
Jordan KR;Loman BR;Bailey MT;Pyter LM
通讯作者：
Pyter LM
一类重要的微生物胆汁酸的生物合成途径。
影响因子：
14.8
作者：
Devlin AS;Fischbach MA
通讯作者：
Fischbach MA
影响因子：
3.9
作者：
Bertelsen, Claus Anders;Larsen, Helene M.;Emmertsen, Katrine J.
通讯作者：
Emmertsen, Katrine J.
影响因子：
1.9
作者：
Kurien, Matthew;Evans, Kate E.;Sanders, David S.
通讯作者：
Sanders, David S.
影响因子：
3.9
作者：
Mulder, Sanna A.;Kranse, Ries;van Leerdam, Monique E.
通讯作者：
van Leerdam, Monique E.