{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:49:45Z","timestamp":1791589785378,"version":"4.3.4"},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Biochemistry &amp;amp; Function"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Colorectal cancer (CRC) continues to be one of the deadliest cancers worldwide, mainly due to late diagnosis, chemoresistance, and the complex interactions within the tumor microenvironment. Recent studies suggest that the gut bacterium\n                    <jats:italic>Akkermansia muciniphila<\/jats:italic>\n                    plays a key role in maintaining intestinal health and may influence the effectiveness of cancer therapies. Therefore, the main aim of this study was to explore whether a lyophilized form of\n                    <jats:italic>A. muciniphila<\/jats:italic>\n                    could support CRC treatment. First, we analyzed\n                    <jats:italic>A. muciniphila<\/jats:italic>\n                    abundance in healthy, adenoma, and CRC tissues using public datasets. Next, CRC cell lines (HT29, HCT116, and SW620) and normal stromal cells (Hs738 St\/Int) were treated with increasing doses of the bacterial extract, alone and with 5\u2010fluorouracil (5\u2010FU). Then, cell viability measured by MTT assay, apoptosis by BAX\/BCL2 expression via RT\u2010qPCR, and physicochemical properties by zeta potential analysis. The results showed a marked reduction of\n                    <jats:italic>A. muciniphila<\/jats:italic>\n                    abundance in CRC samples, with an early decline from healthy to adenoma tissues and a slight recovery in advanced tumors. In vitro, the extract demonstrated dose\u2010dependent cytotoxicity toward cancer cells, with HT29 showing strong sensitivity at low doses, HCT116 responding at higher concentrations, and SW620 exhibiting greater resistance. Importantly, the extract was well tolerated by normal cells, unlike 5\u2010FU. Combining the extract with 5\u2010FU resulted in a synergistic effect, indicating the possibility of reducing 5\u2010FU dosage to limit its toxicity. The extract significantly upregulated BAX, downregulated BCL2, and displayed strong negative zeta potential, supporting enhanced apoptotic activation and selective interaction with cancer cell membranes. These findings suggest that\n                    <jats:italic>A. muciniphila<\/jats:italic>\n                    and its derived products may serve as promising adjuncts in personalized microbiome\u2010based CRC therapy.\n                  <\/jats:p>","DOI":"10.1002\/cbf.70234","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:36:42Z","timestamp":1779255402000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Synergistic Anticancer Effects of\n                    <i>Akkermansia muciniphila<\/i>\n                    Combined With 5\u2010Fluorouracil Through BAX\/BCL2 Dependent Apoptosis in Colorectal Cancer Cells"],"prefix":"10.1002","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3446-7456","authenticated-orcid":false,"given":"Soumaya","family":"Menadi","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Genetics Tokat Gaziosmanpasa University Tokat Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3487-9493","authenticated-orcid":false,"given":"Ercan","family":"Cacan","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics Tokat Gaziosmanpasa University Tokat Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16051029"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10552-019-01181-3"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14122928"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2019.107447"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13402-020-00529-1"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111285"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.adcanc.2024.100114"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.14532"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-020-00811-2"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.955313"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1099\/ijs.0.02873-0"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-022-00650-6"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu17030562"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.934695"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2022.04.135"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41522-022-00338-4"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.4291\/wjgp.v9.i2.47"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1303795"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107278"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0405-7"},{"key":"e_1_2_10_23_1","unstructured":"R Core Team.R: A Language and Environment for Statistical Computing Version 4.3.3. 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