{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T22:26:58Z","timestamp":1790893618938,"version":"4.1.0"},"reference-count":145,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    This review synthesizes recent research findings and proposes an integrated \u201cmicrobiota\u2013metabolite\u2013immune\u2013oncology\u201d framework, highlighting how gut-derived metabolites regulate the dynamics of tumor immunity and informing the development of next-generation immunotherapies. Key metabolites\u2014including short-chain fatty acids (SCFAs), bile acids (BAs), trimethylamine N-oxide (TMAO), indole-3-propionic acid (IPA), and urolithin A\u2014exert bidirectional effects on antitumor immunity through multiple mechanisms. These include histone acetylation-driven epigenetic reprogramming, aryl hydrocarbon receptor (AhR)- and farnesoid X receptor (FXR)-mediated metabolic reprogramming, and direct regulation of immune effectors such as CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells and myeloid-derived suppressor cells. Emerging evidence highlights specific roles of these metabolites within the tumor microenvironment (TME): microbial dysbiosis can amplify immunosuppressive circuits, whereas targeted enrichment of certain metabolites may enhance the efficacy of immune checkpoint blockade. Integrative multi-omics analyses have revealed the vascular remodeling effect of TMAO and the spatiotemporal heterogeneity of BAs, thereby connecting the gut-liver-tumor axis and achieving overall immune regulation. By mapping a precision-oriented metabolic roadmap, this review identifies underexplored therapeutic avenues\u2014such as metabolite-targeted interventions and engineered probiotics\u2014that, when combined with immune checkpoint inhibitors, may enable personalized, microbiome\u2212based strategies with the potential to improve outcomes in cancer immunotherapy.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1882542","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:52:27Z","timestamp":1784699547000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Gut metabolites: key factors in the cross-talk between the gut microbiota and tumor immunotherapy"],"prefix":"10.3389","volume":"17","author":[{"given":"Lizhu","family":"Zeng","sequence":"first","affiliation":[{"name":"School of Clinical Medicine, Chengdu Medical College","place":["Chengdu, Sichuan, 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