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Prot."],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Colorectal cancer (CRC) is one of the most common cancers worldwide. The standard CRC chemo drug, 5-Fluorouracil (5-FU), has a poor response rate and chemoresistance, prompting the need for a more effective and affordable treatment. In this study, we aimed to evaluate whether Prohep, a novel probiotic mixture, would alleviate azoxymethane\/dextran sodium sulfate (AOM\/DSS)-induced colorectal tumorigenesis and enhance 5-FU efficacy and its mechanism. Our results suggested that Prohep showed stronger anti-tumorigenesis effects than 5-FU alone or when combined in the AOM\/DSS model. Prohep significantly reduced the total tumor count, total tumor size, caecum weight, colonic crypt depth, colonic inflammation, and collagen fibrosis. Prohep downregulated pro-inflammatory TNF-\u03b1 and proliferative p-STAT3 and upregulated apoptotic p53. Metagenomics analysis indicated that Prohep-enriched <jats:italic>Helicobacter ganmani<\/jats:italic>, <jats:italic>Desulfovibrio porci<\/jats:italic>, <jats:italic>Helicobacter hepaticus<\/jats:italic>, and <jats:italic>Candidatus Borkfalkia ceftriaxoniphila<\/jats:italic> were inversely correlated to the total tumor count. In addition, Prohep-enriched <jats:italic>Prevotella<\/jats:italic> sp. <jats:italic>PTAC<\/jats:italic> and <jats:italic>Desulfovibrio porci<\/jats:italic> were negatively correlated to AOM\/DSS enriched bacteria, while forming a co-existing community with other beneficial bacteria. From KEGG analysis, Prohep downregulated CRC-related pathways and enhanced pathways related to metabolites suppressing CRC like menaquinone, tetrapyrrole, aminolevulinic acid, and tetrahydrofolate. From Metacyc analysis, Prohep downregulated CRC-related peptidoglycan, LPS, and uric acid biosynthesis, and conversion. Prohep elevated the biosynthesis of the beneficial L-lysine, lipoic acid, pyrimidine, and palmitate. Prohep also elevated metabolic pathways related to energy utilization of lactic acid-producing bacteria (LAB) and acetate producers. Similarly, fecal acetate concentration was upregulated by Prohep. To sum up, Prohep demonstrated exceptional anti-tumorigenesis effects in the AOM\/DSS model, which revealed its potential to develop into a novel CRC therapeutic in the future.<\/jats:p>\n          <jats:p>\n            <jats:bold>Graphical Abstract<\/jats:bold>\n          <\/jats:p>","DOI":"10.1007\/s12602-024-10405-1","type":"journal-article","created":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T03:05:29Z","timestamp":1733454329000},"page":"2227-2243","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Probiotic Mixture Attenuates Colorectal Tumorigenesis in Murine AOM\/DSS Model by Suppressing STAT3, Inducing Apoptotic p53 and Modulating Gut Microbiota"],"prefix":"10.1007","volume":"17","author":[{"given":"Hoi Kit Matthew","family":"Leung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily Kwun Kwan","family":"Lo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congjia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"family":"Felicianna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marsena Jasiel","family":"Ismaiah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hani","family":"El-Nezami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,6]]},"reference":[{"issue":"2","key":"10405_CR1","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1136\/gutjnl-2022-327736","volume":"72","author":"E Morgan","year":"2023","unstructured":"Morgan E et al (2023) Global burden of colorectal cancer in 2020 and 2040: incidence and mortality estimates from GLOBOCAN. 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