{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T04:47:03Z","timestamp":1791953223655,"version":"4.3.4"},"reference-count":57,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Colorectal cancer (CRC) arises within a complex microbial ecosystem that may influence carcinogenesis, tumor immunity, and therapeutic response. This is particularly relevant in metastatic disease, where most tumors are microsatellite-stable\/mismatch repair-proficient (MSS\/pMMR) and derive little meaningful benefit from immune checkpoint inhibitor (ICI) monotherapy. Specific pathobionts, including Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, and colibactin-producing Escherichia coli, have been implicated in genotoxic, inflammatory, and checkpoint-related mechanisms that may contribute to tumor progression and immune evasion, whereas selected commensals and microbiota-derived metabolites may support antitumor immunity in a context-dependent manner. This review integrates translational evidence linking microbial taxa and functions, metabolites, neutrophil biology, bacterial extracellular vesicles, and T-cell dysfunction with CRC progression and immunotherapy response. This review critically examines emerging microbiome-directed strategies, including fecal microbiota transplantation, next-generation probiotics, defined bacterial consortia, dietary and perioperative interventions, postbiotics, and bacteriophage-based approaches, as potential means of modifying immune resistance in MSS\/pMMR CRC. Although early clinical signals from microbiota-modulating combinations are encouraging, the available evidence remains limited by small cohorts, heterogeneous interventions, and the absence of randomized CRC-specific studies. Microbiome-based biomarkers and therapeutics therefore remain investigational, and standardized sampling, prospective validation, and carefully designed trials will be required before microbiome modulation enters routine CRC care.<\/jats:p>","DOI":"10.3390\/cells15191800","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:43:24Z","timestamp":1790880204000},"page":"1800","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Gut Microbiota\u2013Immunity Axis in Colorectal Cancer: Implications for Immunotherapy and Clinical Translation"],"prefix":"10.3390","volume":"15","author":[{"given":"Izabela","family":"Siemi\u0144ska","sequence":"first","affiliation":[{"name":"Department of Clinical Immunology, Institute of Paediatrics, Jagiellonian University Medical College, Wielicka 265, 30-663 Krakow, Poland"},{"name":"Department of Infectious Diseases and Public Health, Faculty of Veterinary Medicine, University of Agriculture in Cracow, 30-059 Krakow, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"ref_1","first-page":"229","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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