{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:29:52Z","timestamp":1791588592787,"version":"4.3.4"},"reference-count":37,"publisher":"Wiley","issue":"25","license":[{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:00:00Z","timestamp":1772150400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","award":["BS2025H005"],"award-info":[{"award-number":["BS2025H005"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Under certain conditions, components of the oral microbiota have been detected in the gastrointestinal tract, implicating oral microbial communities in intestinal immune regulation. However, the mechanisms by which oral microbiota contribute to metastasis at distant organs remain unclear. Here, we demonstrate that the oral bacterium\n                    <jats:italic>Streptococcus salivarius<\/jats:italic>\n                    promotes metastasis of colorectal cancer (CRC) by inducing neutrophil extracellular trap (NET) formation. Mechanistically,\n                    <jats:italic>S. salivarius<\/jats:italic>\n                    induces formation of an IRGM1\u2010IQGAP1 complex in neutrophils, in which immune\u2010related GTPase M1 (IRGM1) interacts with IQ motif\u2010containing GTPase\u2010activating protein 1 (IQGAP1), leading to activation of Wnt5a signaling and subsequent engagement of the PI3K\/AKT pathway, thereby promoting NET formation. Functional validation experiments show that conditional deletion of IRGM1 or pharmacological inhibition of downstream signaling using XAV\u2010939 markedly attenuates\n                    <jats:italic>S. salivarius\u2010<\/jats:italic>\n                    induced NET formation, indicating the requirement of this pathway in the metastatic process. Furthermore, clinical sample analyses reveal that\n                    <jats:italic>S. salivarius<\/jats:italic>\n                    is significantly enriched in the tongue coating and feces of patients with CRC and is elevated within the tumor microenvironment. Together, these findings identify IRGM1\u2010IQGAP1\u2010mediated Wnt5a\u2010PI3K\/AKT signaling as a mechanistic link between oral microbiota and neutrophil\u2010driven immune responses in cancer metastasis.\n                  <\/jats:p>","DOI":"10.1002\/advs.202516546","type":"journal-article","created":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T02:30:52Z","timestamp":1772764252000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Oral\n                    <i>Streptococcus salivarius<\/i>\n                    Couples Neutrophil IRGM1 Signaling to NET Formation and Colorectal Cancer Metastasis"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7289-836X","authenticated-orcid":false,"given":"Fengyi","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Integrated Traditional Chinese and Western Medicine First Affiliated Hospital of Harbin Medical University  Harbin P. R. China"},{"name":"The Key Laboratory of Myocardial Ischemia Chinese Ministry of Education  Harbin P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Wang","sequence":"additional","affiliation":[{"name":"TCM\u2010WM Department The Second Affiliated Hospital of Chongqing Medical University  Chongqing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hengxuan","family":"Cai","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Myocardial Ischemia Chinese Ministry of Education  Harbin P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianwen","family":"Yue","sequence":"additional","affiliation":[{"name":"Collaborative Innovation Center for Genetics and Development State Key Laboratory of Genetic Engineering Shanghai Engineering Research Center of Industrial Microorganisms Department of Microbiology School of Life Sciences Fudan University  Shanghai P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueli","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Integrated Traditional Chinese and Western Medicine First Affiliated Hospital of Harbin Medical University  Harbin P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanwen","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeng","family":"Wang","sequence":"additional","affiliation":[{"name":"The Key Laboratory of Myocardial Ischemia Chinese Ministry of Education  Harbin P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuehan","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Molecular Oncology in Heilongjiang Province  Harbin P. R. 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