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}
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.
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.