{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:56:08Z","timestamp":1790618168566,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"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"}],"funder":[{"DOI":"10.13039\/501100004699","name":"Chung Shan Medical University Hospital","doi-asserted-by":"publisher","award":["CSH\u20102024\u2010C\u2010048"],"award-info":[{"award-number":["CSH\u20102024\u2010C\u2010048"]}],"id":[{"id":"10.13039\/501100004699","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020595","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC 113\u20102320\u2010B\u2010040\u2010008"],"award-info":[{"award-number":["NSTC 113\u20102320\u2010B\u2010040\u2010008"]}],"id":[{"id":"10.13039\/100020595","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    5\u2010fluorouracil (5FU)\u2010induced intestinal mucositis significantly limits its clinical utility and compromises patient outcomes. Building on our previous finding that a specific probiotic formulation, consisting of\n                    <jats:italic>Limosilactobacillus reuteri<\/jats:italic>\n                    BCRC 80379 and\n                    <jats:italic>Clostridium butyricum<\/jats:italic>\n                    MIYAIRI 588 (collectively referred to as LCs), mitigated cisplatin\u2010induced mucositis, this study evaluated the prophylactic efficacy and underlying mechanisms of LCs against 5FU\u2010induced mucositis in Wistar rats. Rats were divided into control, 5FU\u2010only, and 5FU+LCs groups. LCs was orally administered daily for 21 days before and throughout the 5FU treatment (50\u2009mg\/kg\/day for 5 days). Intestinal tissues were analyzed using histological, molecular, and microbiological approaches. Pretreatment with LCs significantly attenuated 5FU\u2010induced small intestinal damage, as evidenced by improved mucosal structure (e.g., increased villus height, crypt depth, and goblet cell density), along with reduced inflammatory cell infiltration. Moreover, LCs reinforced the intestinal barrier by upregulating genes associated with the mucus layer (\n                    <jats:italic>Muc2<\/jats:italic>\n                    ) and tight junctions (\n                    <jats:italic>Ocln<\/jats:italic>\n                    ,\n                    <jats:italic>Tjp1<\/jats:italic>\n                    , and\n                    <jats:italic>Cldn1<\/jats:italic>\n                    ). LCs also suppressed the TLR4\/MyD88\/NF\u2010\u03baB pathway, leading to reduced levels of pro\u2010inflammatory mediators (e.g., TNF\u2010\u03b1, IL\u20101\u03b2, and MPO) while elevating key regulatory mediators such as IL\u201010 and secretory IgA (sIgA). Furthermore, microbial profiling revealed that LCs beneficially reshaped gut microbiota composition by reducing opportunistic pathogens (e.g.,\n                    <jats:italic>Escherichia\u2010Shigella<\/jats:italic>\n                    and\n                    <jats:italic>Enterobacter<\/jats:italic>\n                    ). These microbial changes were accompanied by a favorable immune modulation, including decreased pro\u2010inflammatory markers and increased homeostatic mediators. Collectively, these findings suggest that LCs mitigates 5FU\u2010induced mucositis through coordinated regulation of intestinal barrier integrity, immune responses, and gut microbiota, highlighting its potential as a probiotic\u2010based approach for managing chemotherapy\u2010induced intestinal injury.\n                  <\/jats:p>","DOI":"10.1002\/jcp.70183","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T10:58:26Z","timestamp":1779274706000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Probiotic Combination of\n                    <i>Limosilactobacillus reuteri<\/i>\n                    and\n                    <i>Clostridium butyricum<\/i>\n                    Ameliorates 5\u2010Fluorouracil\u2010Induced Intestinal Mucositis in Rats by Strengthening Barrier Integrity and Modulating Immuno\u2010Microbial Homeostasis"],"prefix":"10.1002","volume":"241","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2220-0903","authenticated-orcid":false,"given":"Pui\u2010Ying","family":"Leong","sequence":"first","affiliation":[{"name":"Division of Allergy, Immunology &amp; Rheumatology, Department of Internal Medicine Chung Shan Medical University Hospital  Taichung Taiwan"},{"name":"School of Medicine Chung Shan Medical University  Taichung Taiwan"},{"name":"Institute of Medicine Chung Shan Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Chen","family":"Chuang","sequence":"additional","affiliation":[{"name":"Department of Nutrition Chung Shan Medical University  Taichung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6855-9239","authenticated-orcid":false,"given":"Jiunn\u2010Liang","family":"Ko","sequence":"additional","affiliation":[{"name":"Institute of Medicine Chung Shan Medical 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Taiwan"},{"name":"Department of Nutrition Chung Shan Medical University Hospital  Taichung 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