{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:33:59Z","timestamp":1792524839483,"version":"4.5.0"},"reference-count":100,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Immune checkpoint inhibitors (ICIs) have transformed the management of microsatellite instability-high\/deficient mismatch repair (MSI-H\/dMMR) colorectal cancer (CRC). However, a substantial proportion of patients exhibit primary resistance or eventually develop acquired resistance, highlighting the need for a better understanding of the biological mechanisms influencing therapeutic response. Increasing evidence suggests that the gut microbiome\u2013immune axis is an important regulator of antitumor immunity through complex interactions among microbial communities, microbial metabolites, host immunity, and the tumor microenvironment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main body<\/jats:title>\n                    <jats:p>This narrative review summarizes current evidence regarding the role of the gut microbiome\u2013immune axis in mediating primary and acquired resistance to immune checkpoint inhibition in MSI-H\/dMMR CRC. We discuss the physiological interactions that maintain immune homeostasis and review the functional mechanisms through which alterations in microbial metabolic pathways, including short-chain fatty acids, bile acids, tryptophan-derived metabolites, inosine, and polyamines, may influence antitumor immune responses. We further examine microbial composition and functional biomarkers associated with immune checkpoint inhibitor response, together with emerging therapeutic strategies aimed at modulating the gut microbiome\u2013immune axis, including dietary interventions, prebiotics, probiotics, selective antimicrobial approaches, fecal microbiota transplantation, live biotherapeutic products, and next-generation precision microbiome engineering. Finally, we discuss current translational challenges and future research priorities required for successful clinical implementation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The gut microbiome\u2013immune axis represents a promising area of investigation for understanding resistance to immune checkpoint inhibition in MSI-H\/dMMR CRC. While growing evidence supports its biological relevance, much of the current knowledge remains preclinical or is derived from early-phase clinical studies. Future progress will depend on mechanistic investigation, longitudinal multi-omic microbiome profiling, standardized methodologies, prospective biomarker validation, and the rational development of microbiome-directed therapeutic strategies to support precision immuno-oncology.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1907957","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:22:24Z","timestamp":1788412944000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Gut microbiome-mediated primary and acquired resistance to immune checkpoint inhibitors in MSI-H\/dMMR colorectal cancer: mechanisms, biomarkers, and therapeutic implications-a narrative review"],"prefix":"10.3389","volume":"16","author":[{"given":"Marko","family":"Marjanovi\u0107","sequence":"first","affiliation":[{"name":"Clinic for Medical Oncology, Oncology Institute of Vojvodina","place":["Sremska Kamenica, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nemanja","family":"Maletin","sequence":"additional","affiliation":[{"name":"Clinic for Medical Oncology, Oncology Institute of Vojvodina","place":["Sremska Kamenica, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biljana","family":"Kuki\u0107","sequence":"additional","affiliation":[{"name":"Clinic for Medical Oncology, Oncology Institute of Vojvodina","place":["Sremska Kamenica, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Nikoli\u0107","sequence":"additional","affiliation":[{"name":"Clinic for Medical Oncology, Oncology Institute of Vojvodina","place":["Sremska Kamenica, Serbia"]},{"name":"Medical Faculty, University of Novi Sad","place":["Novi Sad, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nemanja","family":"Petrovi\u0107","sequence":"additional","affiliation":[{"name":"Clinic for Medical Oncology, Oncology Institute of Vojvodina","place":["Sremska Kamenica, Serbia"]},{"name":"Medical Faculty, University of Novi Sad","place":["Novi Sad, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Radi\u0107","sequence":"additional","affiliation":[{"name":"Clinic for Medical Oncology, Oncology Institute of Vojvodina","place":["Sremska Kamenica, Serbia"]},{"name":"Medical Faculty, University of Novi Sad","place":["Novi Sad, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandar","family":"\u0110uri\u0107","sequence":"additional","affiliation":[{"name":"Clinic for Medical Oncology, Oncology Institute of Vojvodina","place":["Sremska Kamenica, Serbia"]},{"name":"Medical Faculty, University of Novi Sad","place":["Novi Sad, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milica","family":"Knezevi\u0107","sequence":"additional","affiliation":[{"name":"Clinic for Gastroenterology and Hepatology, University Clinical Center of Vojvodina","place":["Novi Sad, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo\u017eidar","family":"Dejanovi\u0107","sequence":"additional","affiliation":[{"name":"Clinic for Gastroenterology and Hepatology, University Clinical Center of Vojvodina","place":["Novi Sad, Serbia"]},{"name":"Medical Faculty, University of Novi Sad","place":["Novi Sad, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanja","family":"\u0106ali\u0107","sequence":"additional","affiliation":[{"name":"Clinic for Gastroenterology and Hepatology, University Clinical Center of Vojvodina","place":["Novi Sad, Serbia"]},{"name":"Medical Faculty, University of Novi Sad","place":["Novi Sad, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctarc.2022.100643","article-title":"Primary and secondary immune checkpoint inhibitors resistance in colorectal cancer: Key mechanisms and ways to overcome resistance","volume":"33","author":"Abushukair","year":"2022","journal-title":"Cancer Treat. Res. Commun."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21176402","article-title":"Gut microbiota and intestinal trans-epithelial permeability","volume":"21","author":"Allam-Ndoul","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1038\/s41422-025-01212-6","article-title":"Gut dysbiosis in oncology: a risk factor for immunoresistance","volume":"36","author":"Almonte","year":"2026","journal-title":"Cell Res."},{"key":"B4","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1016\/j.annonc.2024.03.009","article-title":"Immune checkpoint inhibitors for POLE or POLD1 proofreading-deficient metastatic colorectal cancer","volume":"35","author":"Ambrosini","year":"2024","journal-title":"Ann. Oncol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/s0140-6736(24)02848-4","article-title":"Nivolumab plus ipilimumab versus nivolumab in microsatellite instability-high metastatic colorectal cancer (CheckMate 8HW): a randomised, open-label, phase 3 trial","volume":"405","author":"Andr\u00e9","year":"2025","journal-title":"Lancet"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2207","DOI":"10.1056\/NEJMoa2017699","article-title":"Pembrolizumab in microsatellite-instability-high advanced colorectal cancer","volume":"383","author":"Andr\u00e9","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1126\/science.1224820","article-title":"Intestinal inflammation targets cancer-inducing activity of the microbiota","volume":"338","author":"Arthur","year":"2012","journal-title":"Science"},{"key":"B8","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1126\/science.abb5920","article-title":"Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients","volume":"371","author":"Baruch","year":"2021","journal-title":"Science"},{"key":"B9","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1016\/j.immuni.2017.04.008","article-title":"Homeostatic immunity and the microbiota","volume":"46","author":"Belkaid","year":"2017","journal-title":"Immunity"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1038\/ismej.2012.6","article-title":"Microbes inside-from diversity to function: the case of Akkermansia","volume":"6","author":"Belzer","year":"2012","journal-title":"ISME J."},{"key":"B11","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1038\/s41591-018-0014-x","article-title":"Understanding the tumor immune microenvironment (TIME) for effective therapy","volume":"24","author":"Binnewies","year":"2018","journal-title":"Nat. Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1126\/science.aaf2834","article-title":"Cancer immunology. The 'cancer immunogram'","volume":"352","author":"Blank","year":"2016","journal-title":"Science"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2073","DOI":"10.1053\/j.gastro.2009.12.064","article-title":"Microsatellite instability in colorectal cancer","volume":"138","author":"Boland","year":"2010","journal-title":"Gastroenterology"},{"key":"B14","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1016\/j.clcc.2025.02.003","article-title":"A phase two, single-arm, open-label study with dostarlimab monotherapy in participants with untreated stage II\/III dMMR\/MSI-H locally advanced rectal cancer (AZUR-1)","volume":"24","author":"Cercek","year":"2025","journal-title":"Clin. Colorectal Cancer"},{"key":"B15","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1038\/s41591-020-0805-8","article-title":"Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers","volume":"26","author":"Chalabi","year":"2020","journal-title":"Nat. Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1949","DOI":"10.1056\/nejmoa2400634","article-title":"Neoadjuvant immunotherapy in locally advanced mismatch repair-deficient colon cancer","volume":"390","author":"Chalabi","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/j.canlet.2019.11.019","article-title":"Clostridium butyricum, a butyrate-producing probiotic, inhibits intestinal tumor development through modulating Wnt signaling and gut microbiota","volume":"469","author":"Chen","year":"2020","journal-title":"Cancer Lett."},{"key":"B18","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1038\/nature21349","article-title":"Elements of cancer immunity and the cancer-immune set point","volume":"541","author":"Chen","year":"2017","journal-title":"Nature"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.101355","article-title":"Multi-omics of the gut microbial ecosystem in patients with microsatellite-instability-high gastrointestinal cancer resistant to immunotherapy","volume":"5","author":"Cheng","year":"2024","journal-title":"Cell Rep. Med."},{"key":"B20","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1186\/s12906-019-2528-2","article-title":"Postbiotic metabolites produced by Lactobacillus plantarum strains exert selective cytotoxicity effects on cancer cells","volume":"19","author":"Chuah","year":"2019","journal-title":"BMC Complement Altern. Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"203","DOI":"10.2139\/ssrn.3155839","article-title":"Bacteroides fragilis toxin coordinates a pro-carcinogenic inflammatory cascade via targeting of colonic epithelial cells","volume":"23","author":"Chung","year":"2018","journal-title":"Cell Host Microbe"},{"key":"B22","volume-title":"Fecal Microbiota Transplant and Re-Introduction of Anti-PD-1 Therapy (Pembrolizumab or Nivolumab) for the Treatment of Metastatic Colorectal Cancer in Anti-PD-1 non-Responders","year":"2021"},{"key":"B23","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1016\/j.immuni.2024.02.014","article-title":"Bile acids modified by the intestinal microbiota promote colorectal cancer growth by suppressing CD8+ T-cell effector functions","volume":"57","author":"Cong","year":"2024","journal-title":"Immunity"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1075593","article-title":"Impact of antibiotic use on clinical outcomes of cancer patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis","volume":"13","author":"Crespin","year":"2023","journal-title":"Front. Oncol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1126\/science.abf3363","article-title":"Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients","volume":"371","author":"Davar","year":"2021","journal-title":"Science"},{"key":"B26","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.eururo.2020.04.044","article-title":"Gut bacteria composition drives primary resistance to cancer immunotherapy in renal cell carcinoma patients","volume":"78","author":"Derosa","year":"2020","journal-title":"Eur. Urol."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10051128","article-title":"Faecalibacterium prausnitzii ameliorates colorectal tumorigenesis and suppresses proliferation of HCT116 colorectal cancer cells","volume":"10","author":"Dikeocha","year":"2022","journal-title":"Biomedicines"},{"key":"B28","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1038\/s41573-025-01211-7","article-title":"The gut microbiome as a target in cancer immunotherapy: opportunities and challenges for drug development","volume":"24","author":"Elkrief","year":"2025","journal-title":"Nat. Rev. Drug Discov."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1126\/science.abo2296","article-title":"A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers","volume":"380","author":"Fidelle","year":"2023","journal-title":"Science"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1007\/s00262-018-2150-z","article-title":"Quantifying tumor-infiltrating immune cells from transcriptomics data","volume":"67","author":"Finotello","year":"2018","journal-title":"Cancer Immunol. Immunother."},{"key":"B31","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1158\/2326-6066.cir-16-0297","article-title":"Myeloid-derived suppressor cells","volume":"17","author":"Gabrilovich","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.129216","article-title":"Inulin-based formulations as an emerging therapeutic strategy for cancer: A comprehensive review","volume":"259","author":"Ghali","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1126\/science.aan4236","article-title":"Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients","volume":"359","author":"Gopalakrishnan","year":"2018","journal-title":"Science"},{"key":"B34","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1016\/j.cmet.2021.03.002","article-title":"Gut microbial metabolites facilitate anticancer therapy efficacy by modulating cytotoxic CD8+ T cell immunity","volume":"33","author":"He","year":"2021","journal-title":"Cell Metab."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.1038\/s41590-025-02281-w","article-title":"Microbiota-mediated mechanisms of mucosal immunity across the lifespan","volume":"26","author":"Iliev","year":"2025","journal-title":"Nat. Immunol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1378","DOI":"10.1016\/j.jtho.2019.04.007","article-title":"The diversity of gut microbiome is associated with favorable responses to anti-programmed death 1 immunotherapy in Chinese patients with NSCLC","volume":"14","author":"Jin","year":"2019","journal-title":"J. Thorac. Oncol."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2022.993285","article-title":"Gut microbiota distinct between colorectal cancers with deficient and proficient mismatch repair: A study of 230 CRC patients","volume":"13","author":"Jin","year":"2022","journal-title":"Front. Microbiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/s41577-019-0218-4","article-title":"Tumour-intrinsic resistance to immune checkpoint blockade","volume":"20","author":"Kalbasi","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1038\/s41579-018-0029-9","article-title":"Best practices for analysing microbiomes","volume":"16","author":"Knight","year":"2018","journal-title":"Nat. Rev. Microbiol."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2018.00423","article-title":"Updates in the clinical development of epacadostat and other indoleamine 2,3-dioxygenase 1 inhibitors (IDO1) for human cancers","volume":"8","author":"Komiya","year":"2018","journal-title":"Front. Oncol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.chom.2013.07.007","article-title":"Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment","volume":"14","author":"Kostic","year":"2013","journal-title":"Cell Host Microbe"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1182547","article-title":"Postbiotics in oncology: science or science fiction","volume":"14","author":"Kudra","year":"2023","journal-title":"Front. Microbiol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006440","article-title":"Streptococcus gallolyticus subsp. gallolyticus promotes colorectal tumor development","volume":"13","author":"Kumar","year":"2017","journal-title":"PloS Pathog."},{"key":"B44","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1126\/science.aan6733","article-title":"Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade","volume":"357","author":"Le","year":"2017","journal-title":"Science"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.140940","article-title":"Meta-analysis of the gut microbiota in predicting response to cancer immunotherapy in metastatic melanoma","volume":"5","author":"Limeta","year":"2020","journal-title":"JCI Insight"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2026.1719092","article-title":"Pleiotropic immunoregulation by bile acids in pathophysiology","volume":"17","author":"Lin","year":"2026","journal-title":"Front. Immunol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1158\/2159-8290.cd-14-0863","article-title":"The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints","volume":"5","author":"Llosa","year":"2015","journal-title":"Cancer Discov."},{"key":"B48","doi-asserted-by":"publisher","first-page":"2319","DOI":"10.1038\/s41564-019-0541-3","article-title":"Peptostreptococcus anaerobius promotes colorectal carcinogenesis and modulates tumour immunity","volume":"4","author":"Long","year":"2019","journal-title":"Nat. Microbiol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"10314","DOI":"10.18174\/681298","article-title":"Dietary Lactobacillus rhamnosus GG extracellular vesicles enhance antiprogrammed cell death 1 (anti-PD-1) immunotherapy efficacy against colorectal cancer","volume":"14","author":"Lu","year":"2023","journal-title":"Food Funct."},{"key":"B50","doi-asserted-by":"publisher","first-page":"4077","DOI":"10.1038\/s41467-021-24331-1","article-title":"Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer","volume":"12","author":"Luu","year":"2021","journal-title":"Nat. Commun."},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan5931","article-title":"Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells","volume":"360","author":"Ma","year":"2018","journal-title":"Science"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1481","DOI":"10.1126\/science.abc3421","article-title":"Microbiome-derived inosine modulates response to checkpoint inhibitor immunotherapy","volume":"369","author":"Mager","year":"2020","journal-title":"Science"},{"key":"B53","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/s41592-020-01033-y","article-title":"Method of the year: spatially resolved transcriptomics","volume":"18","author":"Marx","year":"2021","journal-title":"Nat. Methods"},{"key":"B54","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1126\/science.aao3290","article-title":"The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients","volume":"359","author":"Matson","year":"2018","journal-title":"Science"},{"key":"B55","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1038\/s41575-023-00841-9","article-title":"Changing epidemiology of colorectal cancer\u2014birth cohort effects and emerging risk factors","volume":"21","author":"Murphy","year":"2024","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1126\/science.1223813","article-title":"Host-gut microbiota metabolic interactions","volume":"336","author":"Nicholson","year":"2012","journal-title":"Science"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2025.2543124","article-title":"Personalized colorectal cancer risk assessment through explainable AI and gut microbiome profiling","volume":"17","author":"Novielli","year":"2025","journal-title":"Gut Microbes"},{"key":"B58","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/nrgastro.2016.169","article-title":"The intestinal epithelial barrier: a therapeutic target","volume":"14","author":"Odenwald","year":"2017","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1016\/s1470-2045(17)30422-9","article-title":"Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142)","volume":"18","author":"Overman","year":"2017","journal-title":"Lancet Oncol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"6099","DOI":"10.1111\/febs.16086","article-title":"Indoleamine 2,3-dioxygenase 1 (IDO1): an up-to-date overview of an eclectic immunoregulatory enzyme","volume":"289","author":"Pallotta","year":"2022","journal-title":"FEBS J."},{"key":"B61","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1038\/nri.2017.76","article-title":"Single-cell RNA sequencing to explore immune cell heterogeneity","volume":"18","author":"Papalexi","year":"2018","journal-title":"Nat. Rev. Immunol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/s41586-020-2080-8","article-title":"Mutational signature in colorectal cancer caused by genotoxic pks+ Escherichia coli","volume":"580","author":"Pleguezuelos-Manzano","year":"2020","journal-title":"Nature"},{"key":"B63","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1016\/s2468-1253(24)00311-x","article-title":"International consensus statement on microbiome testing in clinical practice","volume":"10","author":"Porcari","year":"2025","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"3294","DOI":"10.1038\/s41467-018-05470-4","article-title":"Microbial tryptophan catabolites in health and disease","volume":"9","author":"Roager","year":"2018","journal-title":"Nat. Commun."},{"key":"B65","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1126\/science.aan3706","article-title":"Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors","volume":"359","author":"Routy","year":"2018","journal-title":"Science"},{"key":"B66","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1038\/s41575-021-00440-6","article-title":"The International Scientific Association of Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of postbiotics","volume":"18","author":"Salminen","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B67","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1093\/oncolo\/oyac162","article-title":"Antibiotic exposure does not impact immune checkpoint blockade response in MSI-H\/dMMR metastatic colorectal cancer: A single-center experience","volume":"27","author":"Serpas Higbie","year":"2022","journal-title":"Oncologist"},{"key":"B68","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/j.cell.2017.01.017","article-title":"Primary, adaptive, and acquired resistance to cancer immunotherapy","volume":"168","author":"Sharma","year":"2017","journal-title":"Cell."},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2019.37.15_suppl.e15169","article-title":"Randomized trial of standard chemotherapy alone or combined with atezolizumab as adjuvant therapy for patients with stage III colon cancer and deficient mismatch repair (ATOMIC, Alliance A021502)","volume":"37","author":"Sinicrope","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1126\/science.aac4255","article-title":"Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy","volume":"350","author":"Sivan","year":"2015","journal-title":"Science"},{"key":"B71","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1186\/s12876-025-04293-0","article-title":"The pathobiont role of Akkermansia muciniphila in colorectal cancer: a systematic review","volume":"25","author":"Soheilipour","year":"2025","journal-title":"BMC Gastroenterol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1186\/s12967-025-06586-0","article-title":"Gut microbiome changes and cancer immunotherapy outcomes associated with dietary interventions: a systematic review of preclinical and clinical evidence","volume":"23","author":"Somodi","year":"2025","journal-title":"J. Transl. Med."},{"key":"B73","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1126\/science.aaz7015","article-title":"Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response","volume":"374","author":"Spencer","year":"2021","journal-title":"Science"},{"key":"B74","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1080\/14796694.2025.2606910","article-title":"A phase III study of perioperative dostarlimab in patients with dMMR\/MSI-H resectable colon cancer: AZUR-2 study design","volume":"22","author":"Starling","year":"2026","journal-title":"Future Oncol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"113495","DOI":"10.1016\/j.annonc.2023.09.1818","article-title":"Immunotherapy in mismatch repair-deficient metastatic colorectal cancer: outcome and novel predictive markers","volume":"198","author":"Stemmer","year":"2024","journal-title":"Eur. J. Cancer"},{"key":"B76","doi-asserted-by":"publisher","first-page":"1127743","DOI":"10.3390\/cells11152296","article-title":"Gut microbiota-derived bile acid metabolites maintain the homeostasis of gut and systemic immunity","volume":"14","author":"Su","year":"2023","journal-title":"Front. Immunol."},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.3322\/caac.70090","article-title":"Global cancer statistics 2024: GLOBOCAN estimates of incidence and mortality worldwide for 34 cancers in 186 countries","author":"Sung","year":"2026","journal-title":"CA Cancer J. Clin"},{"key":"B78","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/j.tim.2020.05.013","article-title":"Microbiome in colorectal cancer: how to get from meta-omics to mechanism","volume":"28","author":"Ternes","year":"2020","journal-title":"Trends Microbiol."},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2019.00016","article-title":"Polyamines and gut microbiota","volume":"6","author":"Tofalo","year":"2019","journal-title":"Front. Nutr."},{"key":"B80","doi-asserted-by":"publisher","first-page":"1246","DOI":"10.1038\/s41590-025-02227-2","article-title":"The role of gut microbial metabolites in the T cell lifecycle","volume":"26","author":"Tran","year":"2025","journal-title":"Nat. Immunol."},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1093\/bib\/bbac443","article-title":"High-resolution shotgun metagenomics: the more data, the better","volume":"23","author":"Tremblay","year":"2022","journal-title":"Brief Bioinform."},{"key":"B82","doi-asserted-by":"publisher","first-page":"8268","DOI":"10.1038\/s41598-019-44753-8","article-title":"The relationship between the structural characteristics of lactobacilli-EPS and its ability to induce apoptosis in colon cancer cells in vitro","volume":"9","author":"Tukenmez","year":"2019","journal-title":"Sci. Rep."},{"key":"B83","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1016\/b978-012078185-0\/50439-x","article-title":"CD8+ T cell states in human cancer: insights from single-cell analysis","volume":"20","author":"van der Leun","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"B84","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1126\/science.aad1329","article-title":"Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota","volume":"350","author":"V\u00e9tizou","year":"2015","journal-title":"Science"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.3390\/nu14153066","article-title":"Probiotics\/Synbiotics to Reduce Infectious Complications after Colorectal Surgery: A Systematic Review and Meta-Analysis of Randomised Controlled Trials","volume":"14","author":"Veziant","year":"2022","journal-title":"Nutrients"},{"key":"B86","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1038\/s42255-020-0219-4","article-title":"Inosine is an alternative carbon source for CD8+-T-cell function under glucose restriction","volume":"2","author":"Wang","year":"2020","journal-title":"Nat. Metab."},{"key":"B87","doi-asserted-by":"publisher","first-page":"690","DOI":"10.1038\/s41575-019-0209-8","article-title":"Gut microbiota in colorectal cancer: mechanisms of action and clinical applications","volume":"16","author":"Wong","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B88","first-page":"1535","article-title":"Role of kynurenine in promoting the generation of exhausted CD8+ T cells in colorectal cancer","volume":"13","author":"Wu","year":"2021","journal-title":"Am. J. Transl. Res."},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2026.102889","article-title":"Dissecting immunosuppressive microenvironment in chemotherapy-resistant colorectal cancer through single-cell transcriptomic analysis","volume":"71","author":"Xi","year":"2026","journal-title":"Transl. Oncol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"1885","DOI":"10.1016\/j.ccell.2025.07.012","article-title":"Tumor-resident probiotic Clostridium butyricum improves aPD-1 efficacy in colorectal cancer models by inhibiting IL-6-mediated immunosuppression","volume":"43","author":"Xie","year":"2025","journal-title":"Cancer Cell."},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2024.1360225","article-title":"Postbiotics in colorectal cancer: intervention mechanisms and perspectives","volume":"15","author":"Xie","year":"2024","journal-title":"Front. Microbiol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"968","DOI":"10.1038\/s41591-019-0458-7","article-title":"Metagenomic and metabolomic analyses reveal distinct stage-specific phenotypes of the gut microbiota in colorectal cancer","volume":"25","author":"Yachida","year":"2019","journal-title":"Nat. Med."},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctcp.2021.101370","article-title":"The effect of pro\/synbiotics on postoperative infections in colorectal cancer patients: A systematic review and meta-analysis","author":"Zeng","year":"2021","journal-title":"Complement Ther. Clin. Pract"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2023.1144534","article-title":"Dynamic gut microbiota changes in patients with advanced Malignancies experiencing secondary resistance to immune checkpoint inhibitors and immune-related adverse events","volume":"13","author":"Zeng","year":"2023","journal-title":"Front. Oncol."},{"key":"B95","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1186\/s40168-019-0767-6","article-title":"Advancing functional and translational microbiome research using meta-omics approaches","volume":"7","author":"Zhang","year":"2019","journal-title":"Microbiome"},{"key":"B96","doi-asserted-by":"publisher","first-page":"4155","DOI":"10.7150\/thno.54476","article-title":"Pectin supplement significantly enhanced the anti-PD-1 efficacy in tumor-bearing mice humanized with gut microbiota from patients with colorectal cancer","volume":"11","author":"Zhang","year":"2021","journal-title":"Theranostics"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2023.102315","article-title":"Fecal microbiota transplantation plus tislelizumab and fruquintinib in refractory microsatellite stable metastatic colorectal cancer: an open-label, single-arm, phase II trial (RENMIN-215)","volume":"66","author":"Zhao","year":"2023","journal-title":"EClinicalMedicine."},{"key":"B98","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.3389\/fphar.2020.611087","article-title":"Anticancer Effects of Weizmannia coagulans MZY531 Postbiotics in CT26 Colorectal Tumor-Bearing Mice by Regulating Apoptosis and Autophagy","volume":"14","author":"Zhong","year":"2024","journal-title":"Life. (Basel)."},{"key":"B99","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1016\/j.cmet.2024.12.013","article-title":"Interplay between gut microbial communities and metabolites modulates pan-cancer immunotherapy responses","volume":"37","author":"Zhu","year":"2025","journal-title":"Cell Metab."},{"key":"B100","doi-asserted-by":"publisher","first-page":"20128","DOI":"10.1038\/s41598-019-56661-y","article-title":"Lysates of Lactobacillus acidophilus combined with CTLA-4-blocking antibodies enhance antitumor immunity in a mouse colon cancer model","volume":"9","author":"Zhuo","year":"2019","journal-title":"Sci. Rep."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1907957\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:22:25Z","timestamp":1788412945000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1907957\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":100,"alternative-id":["10.3389\/fcimb.2026.1907957"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1907957","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]},"article-number":"1907957"}}