肠道微生物群与结直肠癌 CpG 岛甲基化表型之间的关系

IF 12.2 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Gut Microbes Pub Date : 2024-01-01 Epub Date: 2024-06-11 DOI:10.1080/19490976.2024.2363012
Pyoung Hwa Park, Kelsey Keith, Gennaro Calendo, Jaroslav Jelinek, Jozef Madzo, Raad Z Gharaibeh, Jayashri Ghosh, Carmen Sapienza, Christian Jobin, Jean-Pierre J Issa
{"title":"肠道微生物群与结直肠癌 CpG 岛甲基化表型之间的关系","authors":"Pyoung Hwa Park, Kelsey Keith, Gennaro Calendo, Jaroslav Jelinek, Jozef Madzo, Raad Z Gharaibeh, Jayashri Ghosh, Carmen Sapienza, Christian Jobin, Jean-Pierre J Issa","doi":"10.1080/19490976.2024.2363012","DOIUrl":null,"url":null,"abstract":"<p><p>The intestinal microbiota is an important environmental factor implicated in CRC development. Intriguingly, modulation of DNA methylation by gut microbiota has been reported in preclinical models, although the relationship between tumor-infiltrating bacteria and CIMP status is currently unexplored. In this study, we investigated tumor-associated bacteria in 203 CRC tumor cases and validated the findings using The Cancer Genome Atlas datasets. We assessed the abundance of <i>Bacteroides fragilis</i>, <i>Escherichia coli</i>, <i>Fusobacterium nucleatum</i>, and <i>Klebsiella pneumoniae</i> through qPCR analysis and observed enrichment of all four bacterial species in CRC samples. Notably, except for <i>E. coli</i>, all exhibited significant enrichment in cases of CIMP. This enrichment was primarily driven by a subset of cases distinguished by high levels of these bacteria, which we labeled as \"Superhigh\". The bacterial Superhigh status showed a significant association with CIMP (odds ratio 3.1, p-value = 0.013) and with <i>MLH1</i> methylation (odds ratio 4.2, p-value = 0.0025). In TCGA CRC cases (393 tumor and 45 adj. normal), bacterial taxa information was extracted from non-human whole exome sequencing reads, and the bacterial Superhigh status was similarly associated with CIMP (odds ratio 2.9, <i>p</i> < 0.001) and <i>MLH1</i> methylation (odds ratio 3.5, <i>p</i> < 0.001). Finally, 16S ribosomal RNA gene sequencing revealed high enrichment of <i>Bergeyella spp</i>. <i>C. concisus</i>, and <i>F. canifelinum</i> in CIMP-Positive tumor cases. Our findings highlight that specific bacterial taxa may influence DNA methylation, particularly in CpG islands, and contribute to the development and progression of CIMP in colorectal cancer.</p>","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"16 1","pages":"2363012"},"PeriodicalIF":12.2000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11174071/pdf/","citationCount":"0","resultStr":"{\"title\":\"Association between gut microbiota and CpG island methylator phenotype in colorectal cancer.\",\"authors\":\"Pyoung Hwa Park, Kelsey Keith, Gennaro Calendo, Jaroslav Jelinek, Jozef Madzo, Raad Z Gharaibeh, Jayashri Ghosh, Carmen Sapienza, Christian Jobin, Jean-Pierre J Issa\",\"doi\":\"10.1080/19490976.2024.2363012\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The intestinal microbiota is an important environmental factor implicated in CRC development. Intriguingly, modulation of DNA methylation by gut microbiota has been reported in preclinical models, although the relationship between tumor-infiltrating bacteria and CIMP status is currently unexplored. In this study, we investigated tumor-associated bacteria in 203 CRC tumor cases and validated the findings using The Cancer Genome Atlas datasets. We assessed the abundance of <i>Bacteroides fragilis</i>, <i>Escherichia coli</i>, <i>Fusobacterium nucleatum</i>, and <i>Klebsiella pneumoniae</i> through qPCR analysis and observed enrichment of all four bacterial species in CRC samples. Notably, except for <i>E. coli</i>, all exhibited significant enrichment in cases of CIMP. This enrichment was primarily driven by a subset of cases distinguished by high levels of these bacteria, which we labeled as \\\"Superhigh\\\". The bacterial Superhigh status showed a significant association with CIMP (odds ratio 3.1, p-value = 0.013) and with <i>MLH1</i> methylation (odds ratio 4.2, p-value = 0.0025). In TCGA CRC cases (393 tumor and 45 adj. normal), bacterial taxa information was extracted from non-human whole exome sequencing reads, and the bacterial Superhigh status was similarly associated with CIMP (odds ratio 2.9, <i>p</i> < 0.001) and <i>MLH1</i> methylation (odds ratio 3.5, <i>p</i> < 0.001). Finally, 16S ribosomal RNA gene sequencing revealed high enrichment of <i>Bergeyella spp</i>. <i>C. concisus</i>, and <i>F. canifelinum</i> in CIMP-Positive tumor cases. Our findings highlight that specific bacterial taxa may influence DNA methylation, particularly in CpG islands, and contribute to the development and progression of CIMP in colorectal cancer.</p>\",\"PeriodicalId\":12909,\"journal\":{\"name\":\"Gut Microbes\",\"volume\":\"16 1\",\"pages\":\"2363012\"},\"PeriodicalIF\":12.2000,\"publicationDate\":\"2024-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11174071/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Gut Microbes\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/19490976.2024.2363012\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/6/11 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gut Microbes","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/19490976.2024.2363012","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/6/11 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

肠道微生物群是与癌症发病有关的重要环境因素。有趣的是,临床前模型中已经报道了肠道微生物群对 DNA 甲基化的调节作用,但目前尚未探讨肿瘤浸润细菌与 CIMP 状态之间的关系。在本研究中,我们调查了 203 例 CRC 肿瘤病例中的肿瘤相关细菌,并利用癌症基因组图谱数据集验证了研究结果。我们通过 qPCR 分析评估了脆弱拟杆菌(Bacteroides fragilis)、大肠杆菌(Escherichia coli)、核酸镰刀菌(Fusobacterium nucleatum)和肺炎克雷伯菌(Klebsiella pneumoniae)的丰度,并观察到这四种细菌在 CRC 样本中都有富集。值得注意的是,除大肠杆菌外,其他细菌在 CIMP 病例中都表现出明显的富集。这种富集主要是由病例中的一个子集引起的,该子集的细菌含量很高,我们将其称为 "超高"。细菌超高状态与 CIMP(几率比 3.1,p 值 = 0.013)和 MLH1 甲基化(几率比 4.2,p 值 = 0.0025)有显著关联。在 TCGA CRC 病例(393 例肿瘤病例和 45 例辅助正常病例)中,从非人全外显子组测序读数中提取了细菌类群信息,细菌超高状态与 CIMP 相似(几率比 2.9,p MLH1 甲基化(几率比 3.5,p Bergeyella spp. C. concisus 和 F. canifelinum 在 CIMP 阳性肿瘤病例中)。我们的研究结果表明,特定的细菌类群可能会影响 DNA 甲基化,尤其是 CpG 岛,并导致结直肠癌 CIMP 的发生和发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Association between gut microbiota and CpG island methylator phenotype in colorectal cancer.

The intestinal microbiota is an important environmental factor implicated in CRC development. Intriguingly, modulation of DNA methylation by gut microbiota has been reported in preclinical models, although the relationship between tumor-infiltrating bacteria and CIMP status is currently unexplored. In this study, we investigated tumor-associated bacteria in 203 CRC tumor cases and validated the findings using The Cancer Genome Atlas datasets. We assessed the abundance of Bacteroides fragilis, Escherichia coli, Fusobacterium nucleatum, and Klebsiella pneumoniae through qPCR analysis and observed enrichment of all four bacterial species in CRC samples. Notably, except for E. coli, all exhibited significant enrichment in cases of CIMP. This enrichment was primarily driven by a subset of cases distinguished by high levels of these bacteria, which we labeled as "Superhigh". The bacterial Superhigh status showed a significant association with CIMP (odds ratio 3.1, p-value = 0.013) and with MLH1 methylation (odds ratio 4.2, p-value = 0.0025). In TCGA CRC cases (393 tumor and 45 adj. normal), bacterial taxa information was extracted from non-human whole exome sequencing reads, and the bacterial Superhigh status was similarly associated with CIMP (odds ratio 2.9, p < 0.001) and MLH1 methylation (odds ratio 3.5, p < 0.001). Finally, 16S ribosomal RNA gene sequencing revealed high enrichment of Bergeyella spp. C. concisus, and F. canifelinum in CIMP-Positive tumor cases. Our findings highlight that specific bacterial taxa may influence DNA methylation, particularly in CpG islands, and contribute to the development and progression of CIMP in colorectal cancer.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Gut Microbes
Gut Microbes Medicine-Microbiology (medical)
CiteScore
18.20
自引率
3.30%
发文量
196
审稿时长
10 weeks
期刊介绍: The intestinal microbiota plays a crucial role in human physiology, influencing various aspects of health and disease such as nutrition, obesity, brain function, allergic responses, immunity, inflammatory bowel disease, irritable bowel syndrome, cancer development, cardiac disease, liver disease, and more. Gut Microbes serves as a platform for showcasing and discussing state-of-the-art research related to the microorganisms present in the intestine. The journal emphasizes mechanistic and cause-and-effect studies. Additionally, it has a counterpart, Gut Microbes Reports, which places a greater focus on emerging topics and comparative and incremental studies.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信