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Following the notion that perinatal bacterial exposure might confer immune system competency for life, we investigated whether early\u2010life administration of cholera\u2010toxin (CT), a protein exotoxin of the small intestine pathogenic bacterium <jats:italic>Vibrio cholerae<\/jats:italic>, may shape local and systemic immunity to impart a protective effect against tumor development in epithelia distantly located from the gut. For that, newborn mice were orally treated with low non\u2010pathogenic doses of CT and later challenged with the carcinogen 7,12\u2010dimethylbenzanthracene (DMBA), known to cause mainly mammary, but also skin, lung and stomach cancer. Our results revealed that CT suppressed the overall incidence and multiplicity of tumors, with varying efficiencies among cancer types, and promoted survival. Harvesting mouse tissues at an earlier time\u2010point (105 instead of 294\u2009days), showed that CT does not prevent preneoplastic lesions per se but it rather hinders their evolution into tumors. CT pretreatment universally increased apoptosis in the cancer\u2010prone mammary, lung and nonglandular stomach, and altered the expression of several cancer\u2010related molecules. Moreover, CT had a long\u2010term effect on immune system cells and factors, the most prominent being the systemic neutrophil decrease. Finally, CT treatment significantly affected gut bacterial flora composition, leading among others to a major shift from <jats:italic>Clostridia<\/jats:italic> to <jats:italic>Bacilli<\/jats:italic> class abundance. Overall, these results support the notion that early\u2010life CT consumption is able to affect host's immune, microbiome and gene expression profiles toward the prevention of cancer.<\/jats:p>","DOI":"10.1002\/ijc.34816","type":"journal-article","created":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T14:18:50Z","timestamp":1702563530000},"page":"1097-1110","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Peri\u2010weaning cholera toxin consumption suppresses chemically\u2010induced carcinogenesis in mice"],"prefix":"10.1002","volume":"154","author":[{"given":"Hara","family":"Afaloniati","sequence":"first","affiliation":[{"name":"Laboratory of Biochemistry and Toxicology, School of Veterinary Medicine, Faculty of Health Sciences Aristotle University of Thessaloniki  Thessaloniki 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