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Here, using chronic restraint stress (CRS) in male mice, we show that stress increases metastatic burden and reduces survival in lung metastasis and peritoneal dissemination models, while also increasing overall tumor burden in an orthotopic gastric cancer model. Single\u2010cell transcriptomics of lung metastases reveals stress\u2010associated remodeling of tumor\u2010associated macrophages toward immunosuppressive states, while macrophage depletion attenuates stress\u2010enhanced metastasis. Stress also reshapes the gut microbiota and enriches\n                    <jats:italic>Lactobacillus reuteri<\/jats:italic>\n                    , and microbiota transfer, antibiotic treatment, co\u2010housing, and bacterial gavage experiments support a microbiota\u2010dependent contribution to metastatic progression. Metabolomic analyses identify kynurenine as a stress\u2010 and\n                    <jats:italic>L. reuteri<\/jats:italic>\n                    \u2010associated tryptophan metabolite that promotes macrophage\u2010dependent dissemination, whereas tryptophan deficiency blunts stress\u2010 and\n                    <jats:italic>L. reuteri<\/jats:italic>\n                    \u2010enhanced metastasis. Mechanistically, our data support a role for TNFR2\u2013C\/EBP\u03b2 signaling in Kyn\u2010induced immunosuppressive macrophage remodeling. In clinical gastric cancer cohorts, higher depressive symptom burden is associated with shorter disease\u2010free survival,\n                    <jats:italic>Lactobacillus<\/jats:italic>\n                    enrichment, elevated plasma Kyn\/Trp ratio, and altered macrophage phenotypes. Together, these findings define a stress\u2013microbiota\u2013tryptophan metabolism\u2013macrophage axis that links chronic stress to gastric cancer metastasis in male mouse models and clinical samples.\n                  <\/jats:p>","DOI":"10.1002\/advs.77612","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:01:01Z","timestamp":1788498061000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic Stress Promotes Gastric Cancer Metastasis by Inducing Microbiota\u2010Associated Kynurenine Accumulation and Macrophage Remodeling"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5213-1146","authenticated-orcid":false,"given":"Sicheng","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences Zhejiang Chinese Medical University  Hangzhou China"},{"name":"Key Laboratory of Blood\u2010Stasis\u2010Toxin Syndrome of Zhejiang 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Laboratory of Blood\u2010Stasis\u2010Toxin Syndrome of Zhejiang Province  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1096-7148","authenticated-orcid":false,"given":"Shuo","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Zhejiang Chinese Medical University  Hangzhou China"},{"name":"Key Laboratory of Blood\u2010Stasis\u2010Toxin Syndrome of Zhejiang Province  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4214-4136","authenticated-orcid":false,"given":"Boqiang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University  Hangzhou China"},{"name":"National Engineering Research Center of Innovation and Application of Minimally Invasive Instruments  Hangzhou China"},{"name":"Zhejiang Minimal Invasive Diagnosis and Treatment Technology Research Center of Severe Hepatobiliary Disease Sir Run Run Shaw Hospital School of Medicine Zhejiang University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhai","family":"Wei","sequence":"additional","affiliation":[{"name":"Huzhou Central Hospital Fifth School of Clinical Medicine of Zhejiang Chinese Medical University  Huzhou China"},{"name":"Huzhou Central Hospital Affiliated Central Hospital of Huzhou University  Huzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengmei","family":"Qiu","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences Zhejiang Chinese Medical University  Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7821-2076","authenticated-orcid":false,"given":"Tao","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences Zhejiang Chinese Medical University 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