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Although these signatures are present in established tumors, growing evidence suggests that colibactin acts early in tumorigenesis, positioning pks+ E. coli as a potential contributor to CRC initiation. Mechanistic studies show that colibactin genotoxicity is highly context dependent and requires direct epithelial contact\u2014a condition that is typically restricted in the healthy adult intestine. Here, we propose that colibactin mutagenesis occurs during discrete temporal windows when host barriers and microbial ecology transiently permit pks+ E. coli-epithelial interactions. These windows may arise during inflammatory disease states or early-life gut development, two contexts that share disrupted epithelial defenses, expansion of facultative anaerobes, and dynamic oxygen gradients. Defining such permissive states will be essential for establishing causal links between pks+ E. coli exposure and CRC initiation and may reveal opportunities for prevention by targeting microbial colonization during critical periods of susceptibility.<\/jats:p>","DOI":"10.1093\/jambio\/lxag192","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T11:16:05Z","timestamp":1785323765000},"source":"Crossref","is-referenced-by-count":0,"title":["Windows of opportunity for genotoxic\n                    <i>E. coli<\/i>\n                    in colorectal cancer initiation"],"prefix":"10.1093","volume":"137","author":[{"given":"Jarryd Michael","family":"Boath","sequence":"first","affiliation":[{"name":"Junior Research Group Epithelium Microbiome Interactions (EMIL), German Cancer Research Center , Heidelberg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi Lukas","family":"Nardella","sequence":"additional","affiliation":[{"name":"Junior Research Group Epithelium Microbiome Interactions (EMIL), German Cancer Research Center , Heidelberg ,","place":["Germany"]},{"name":"Faculty of Biosciences, Heidelberg University , Heidelberg ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9275-4034","authenticated-orcid":false,"given":"Jens","family":"Puschhof","sequence":"additional","affiliation":[{"name":"Junior Research Group Epithelium Microbiome Interactions (EMIL), German Cancer Research Center , Heidelberg ,","place":["Germany"]},{"name":"Faculty of Biosciences, Heidelberg University , Heidelberg ,","place":["Germany"]},{"name":"DKFZ Hector Cancer Institute at the University Medical Center Mannheim ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"2026101409275957100_bib1","doi-asserted-by":"crossref","DOI":"10.1099\/mic.0.001427","article-title":"Current understandings of colibactin regulation","volume":"170","author":"Addington","year":"2024","journal-title":"Microbiology (Reading)"},{"key":"2026101409275957100_bib2","doi-asserted-by":"publisher","first-page":"1539595","DOI":"10.1080\/21688370.2018.1539595","article-title":"Role of gut microbiota in intestinal wound healing and barrier function","volume":"6","author":"Alam","year":"2018","journal-title":"Tissue Barriers"},{"key":"2026101409275957100_bib3","doi-asserted-by":"publisher","first-page":"862","DOI":"10.1053\/j.gastro.2022.06.054","article-title":"Western-style diet, pks island-carrying Escherichia coli, and colorectal cancer: analyses from two large prospective cohort studies","volume":"163","author":"Arima","year":"2022","journal-title":"Gastroenterology"},{"key":"2026101409275957100_bib4","doi-asserted-by":"publisher","first-page":"4724","DOI":"10.1038\/ncomms5724","article-title":"Microbial genomic analysis reveals the essential role of inflammation in bacteria-induced colorectal cancer","volume":"5","author":"Arthur","year":"2014","journal-title":"Nat Commun"},{"key":"2026101409275957100_bib5","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1126\/science.1224820","article-title":"Intestinal inflammation targets cancer-inducing activity of the microbiota","volume":"338","author":"Arthur","year":"2012","journal-title":"Science"},{"key":"2026101409275957100_bib6","doi-asserted-by":"publisher","first-page":"2222437","DOI":"10.1080\/19490976.2023.2222437","article-title":"Oxygen concentration modulates colibactin production","volume":"15","author":"Bossuet","year":"2023","journal-title":"Gut Microbes"},{"key":"2026101409275957100_bib7","doi-asserted-by":"publisher","first-page":"e56964","DOI":"10.1371\/journal.pone.0056964","article-title":"High prevalence of mucosa-associated E. coli producing cyclomodulin and genotoxin in colon cancer","volume":"8","author":"Buc","year":"2013","journal-title":"PLoS One"},{"key":"2026101409275957100_bib8","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1016\/j.tim.2022.05.010","article-title":"The pks island: a bacterial Swiss army knife? 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