{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:02:05Z","timestamp":1790010125286,"version":"4.0.1"},"reference-count":91,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["RF-2024-12376973"],"award-info":[{"award-number":["RF-2024-12376973"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Immune checkpoint inhibitors (ICIs) have transformed the treatment of several malignancies, but their efficacy and gastrointestinal (GI) immune-related adverse events (irAEs) vary considerably among patients. Growing evidence suggests that the gut microbiota and intestinal barrier integrity are associated with both therapeutic response and toxicity, although their causal contribution and clinical utility remain incompletely defined. Dysbiosis may disrupt epithelial homeostasis, increase intestinal permeability, and promote mucosal immune activation, potentially influencing antitumor immunity and susceptibility to ICI-induced colitis. Current biomarkers of intestinal permeability are limited by their indirect nature, lack of standardization, or poor spatial resolution. Probe-based confocal laser endomicroscopy (pCLE) enables real-time, in vivo visualization of epithelial abnormalities associated with barrier dysfunction, including fluorescein leakage, epithelial gaps, and cell shedding. In parallel, dietary and microbiota-directed interventions are being investigated as potential strategies to modulate intestinal homeostasis during ICI therapy, although evidence for their clinical benefit and effects on intestinal barrier integrity remains limited. This review summarizes current evidence linking the gut microbiota, intestinal barrier dysfunction, and cancer immunotherapy and discusses the potential role of pCLE as a candidate functional imaging tool in ICI-treated patients. We highlight current knowledge gaps and propose a translational framework integrating pCLE with microbiome profiling, circulating biomarkers, histopathology, and clinical outcomes to determine whether this approach can improve patient stratification and the early identification and monitoring of GI toxicity.<\/jats:p>","DOI":"10.3390\/nu18183086","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T12:50:03Z","timestamp":1789995003000},"page":"3086","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Probe-Based Confocal Laser Endomicroscopy During Immune Checkpoint Inhibitor Therapy: A Translational Framework Linking Intestinal Barrier Function, Microbiota, and Clinical Outcomes"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3033-404X","authenticated-orcid":false,"given":"Paola","family":"Spessotto","sequence":"first","affiliation":[{"name":"Molecular Oncology Unit, Centro di Riferimento Oncologico Aviano, (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Orbosu\u00e8","sequence":"additional","affiliation":[{"name":"Oncological Gastroenterology Unit, Department of Medical Oncology, Centro di Riferimento Oncologico Aviano, (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6509-0068","authenticated-orcid":false,"given":"Maurizio","family":"Mongiat","sequence":"additional","affiliation":[{"name":"Molecular Oncology Unit, Centro di Riferimento Oncologico Aviano, (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Maiero","sequence":"additional","affiliation":[{"name":"Oncological Gastroenterology Unit, Department of Medical Oncology, Centro di Riferimento Oncologico Aviano, (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Sartori","sequence":"additional","affiliation":[{"name":"Oncological Gastroenterology Unit, Department of Medical Oncology, Centro di Riferimento Oncologico Aviano, (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5052-3502","authenticated-orcid":false,"given":"Michela","family":"Guardascione","sequence":"additional","affiliation":[{"name":"Medical Oncology and Cancer Prevention, Department of Medical Oncology, Centro di Riferimento Oncologico Aviano, (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Foltran","sequence":"additional","affiliation":[{"name":"Medical Oncology and Cancer Prevention, Department of Medical Oncology, Centro di Riferimento Oncologico Aviano, (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Fumagalli","sequence":"additional","affiliation":[{"name":"Medical Oncology and Cancer Prevention, Department of Medical Oncology, Centro di Riferimento Oncologico Aviano, (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1219-029X","authenticated-orcid":false,"given":"Marco","family":"de Scordilli","sequence":"additional","affiliation":[{"name":"Medical Oncology and Cancer Prevention, Department of Medical Oncology, Centro di Riferimento Oncologico Aviano, (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1020-2338","authenticated-orcid":false,"given":"Alessandra","family":"Bearz","sequence":"additional","affiliation":[{"name":"Medical Oncology and Immune-Related Tumors, Department of Medical Oncology, Centro di Riferimento Oncologico Aviano, (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Fratino","sequence":"additional","affiliation":[{"name":"Medical Oncology and Immune-Related Tumors, Department of Medical Oncology, Centro di Riferimento Oncologico Aviano, (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Bolzonello","sequence":"additional","affiliation":[{"name":"Medical Oncology and Cancer Prevention, Department of Medical Oncology, Centro di Riferimento Oncologico Aviano, (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Spina","sequence":"additional","affiliation":[{"name":"Medical Oncology and Immune-Related Tumors, Department of Medical Oncology, Centro di Riferimento Oncologico Aviano, (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0573-4938","authenticated-orcid":false,"given":"Fabio","family":"Puglisi","sequence":"additional","affiliation":[{"name":"Medical Oncology and Cancer Prevention, Department of Medical Oncology, Centro di Riferimento Oncologico Aviano, (CRO) IRCCS, 33081 Aviano, Italy"},{"name":"Department of Medicine, University of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6010-0976","authenticated-orcid":false,"given":"Vincenzo","family":"Canzonieri","sequence":"additional","affiliation":[{"name":"Pathology Unit, Centro di Riferimento Oncologico Aviano, (CRO) IRCCS, 33081 Aviano, Italy"},{"name":"Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2020-222X","authenticated-orcid":false,"given":"Renato","family":"Cannizzaro","sequence":"additional","affiliation":[{"name":"Oncological Gastroenterology Unit, Department of Medical Oncology, Centro di Riferimento Oncologico Aviano, (CRO) IRCCS, 33081 Aviano, Italy"},{"name":"Department of Medical, Surgical and Health Sciences, University of Trieste, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1625-9853","authenticated-orcid":false,"given":"Riccardo","family":"Dolcetti","sequence":"additional","affiliation":[{"name":"Peter MacCallum Cancer Center, Melbourne, VIC 3000, Australia"},{"name":"Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC 3010, Australia"},{"name":"Department of Microbiology and Immunology, The University of Melbourne, Melbourne, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0548-7092","authenticated-orcid":false,"given":"Elena","family":"Ongaro","sequence":"additional","affiliation":[{"name":"Medical Oncology and Cancer Prevention, Department of Medical Oncology, Centro di Riferimento Oncologico Aviano, (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6843-7637","authenticated-orcid":false,"given":"Stefano","family":"Realdon","sequence":"additional","affiliation":[{"name":"Oncological Gastroenterology Unit, Department of Medical Oncology, Centro di Riferimento Oncologico Aviano, (CRO) IRCCS, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"100336","DOI":"10.1016\/j.esmoop.2021.100336","article-title":"Real-World Application of Tumor Mutational Burden-High (TMB-High) and Microsatellite Instability (MSI) Confirms Their Utility as Immunotherapy Biomarkers","volume":"7","author":"Palmeri","year":"2022","journal-title":"ESMO Open"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1080\/14712598.2017.1315405","article-title":"Immunotherapy for Colorectal Cancer: Where Are We Heading?","volume":"17","author":"Basile","year":"2017","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1080\/17512433.2017.1313113","article-title":"Immunotherapy for Gastric Cancers: Emerging Role and Future Perspectives","volume":"10","author":"Bonotto","year":"2017","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1158\/2159-8290.CD-15-1545","article-title":"Analysis of Immune Signatures in Longitudinal Tumor Samples Yields Insight into Biomarkers of Response and Mechanisms of Resistance to Immune Checkpoint Blockade","volume":"6","author":"Chen","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"S87","DOI":"10.3747\/co.27.5223","article-title":"A Review of Cancer Immunotherapy: From the Past, to the Present, to the Future","volume":"27","author":"Esfahani","year":"2020","journal-title":"Curr. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1056\/NEJMra1703481","article-title":"Immune-Related Adverse Events Associated with Immune Checkpoint Blockade","volume":"378","author":"Postow","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1053\/j.gastro.2020.08.063","article-title":"AGA Clinical Practice Update on Diagnosis and Management of Immune Checkpoint Inhibitor Colitis and Hepatitis: Expert Review","volume":"160","author":"Dougan","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/s41571-022-00600-w","article-title":"Immune-Checkpoint Inhibitors: Long-Term Implications of Toxicity","volume":"19","author":"Johnson","year":"2022","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1001\/jamaoncol.2018.3923","article-title":"Fatal Toxic Effects Associated with Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis","volume":"4","author":"Wang","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e000585","DOI":"10.1136\/esmoopen-2019-000585","article-title":"Five-Year Review of Corticosteroid Duration and Complications in the Management of Immune Checkpoint Inhibitor-Related Diarrhoea and Colitis in Advanced Melanoma","volume":"5","author":"Favara","year":"2020","journal-title":"ESMO Open"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3373","DOI":"10.1016\/j.cell.2024.05.029","article-title":"Custom Scoring Based on Ecological Topology of Gut Microbiota Associated with Cancer Immunotherapy Outcome","volume":"187","author":"Derosa","year":"2024","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","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":"ref_13","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1038\/s41591-024-02823-z","article-title":"A Gut Microbial Signature for Combination Immune Checkpoint Blockade across Cancer Types","volume":"30","author":"Gunjur","year":"2024","journal-title":"Nat. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/s13073-021-00923-w","article-title":"Role of the Intestinal Microbiome and Microbial-Derived Metabolites in Immune Checkpoint Blockade Immunotherapy of Cancer","volume":"13","author":"Hayase","year":"2021","journal-title":"Genome Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1432","DOI":"10.1038\/s41591-021-01406-6","article-title":"Gut Microbiota Signatures Are Associated with Toxicity to Combined CTLA-4 and PD-1 Blockade","volume":"27","author":"Andrews","year":"2021","journal-title":"Nat. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1038\/s41467-020-16079-x","article-title":"Systemic Short Chain Fatty Acids Limit Antitumor Effect of CTLA-4 Blockade in Hosts with Cancer","volume":"11","author":"Coutzac","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1016\/j.neo.2017.08.004","article-title":"Metagenomic Shotgun Sequencing and Unbiased Metabolomic Profiling Identify Specific Human Gut Microbiota and Metabolites Associated with Immune Checkpoint Therapy Efficacy in Melanoma Patients","volume":"19","author":"Frankel","year":"2017","journal-title":"Neoplasia"},{"key":"ref_18","first-page":"60","article-title":"Gut Microecology Empowers Cancer Immunotherapy: Commensal Microbiota-Mediated Mechanisms and Translational Prospects of PD-1\/PD-L1 Therapy","volume":"23","author":"Li","year":"2026","journal-title":"Cancer Biol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"23","DOI":"10.32604\/or.2025.072661","article-title":"Gut Associated Metabolites Enhance PD-L1 Blockade Efficacy in Prostate Cancer","volume":"34","author":"Liu","year":"2026","journal-title":"Oncol. Res."},{"key":"ref_20","doi-asserted-by":"crossref","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":"ref_21","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s41577-024-01014-8","article-title":"Short-Chain Fatty Acids: Linking Diet, the Microbiome and Immunity","volume":"24","author":"Mann","year":"2024","journal-title":"Nat. Rev. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Parada Venegas, D., De la Fuente, M.K., Landskron, G., Gonz\u00e1lez, M.J., Quera, R., Dijkstra, G., Harmsen, H.J.M., Faber, K.N., and Hermoso, M.A. (2019). Short Chain Fatty Acids (SCFAs)-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01486"},{"key":"ref_23","doi-asserted-by":"crossref","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":"ref_24","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1038\/s41591-025-04186-5","article-title":"Fecal Microbiota Transplantation plus Immunotherapy in Non-Small Cell Lung Cancer and Melanoma: The Phase 2 FMT-LUMINate Trial","volume":"32","author":"Duttagupta","year":"2026","journal-title":"Nat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/S2468-1253(24)00390-X","article-title":"The Intestinal Barrier: A Pivotal Role in Health, Inflammation, and Cancer","volume":"10","author":"Neurath","year":"2025","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e450","DOI":"10.1038\/emm.2017.282","article-title":"Akkermansia Muciniphila-Derived Extracellular Vesicles Influence Gut Permeability through the Regulation of Tight Junctions","volume":"50","author":"Chelakkot","year":"2018","journal-title":"Exp. Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/nri3608","article-title":"Intestinal Epithelial Cells: Regulators of Barrier Function and Immune Homeostasis","volume":"14","author":"Peterson","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1136\/gutjnl-2023-331579","article-title":"Opening the Doors of Precision Medicine: Novel Tools to Assess Intestinal Barrier in Inflammatory Bowel Disease and Colitis-Associated Neoplasia","volume":"73","author":"Iacucci","year":"2024","journal-title":"Gut"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"102406","DOI":"10.1016\/j.ctrv.2022.102406","article-title":"The Gut Wall\u2019s Potential as a Partner for Precision Oncology in Immune Checkpoint Treatment","volume":"107","author":"Jalving","year":"2022","journal-title":"Cancer Treat. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"537170","DOI":"10.1155\/2012\/537170","article-title":"Endomicroscopy and Cancer: A New Approach to the Visualization of Neoangiogenesis","volume":"2012","author":"Cannizzaro","year":"2012","journal-title":"Gastroenterol. Res. Pract."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Capuano, A., Andreuzzi, E., Pivetta, E., Doliana, R., Favero, A., Canzonieri, V., Maiero, S., Fornasarig, M., Magris, R., and Cannizzaro, R. (2019). The Probe Based Confocal Laser Endomicroscopy (pCLE) in Locally Advanced Gastric Cancer: A Powerful Technique for Real-Time Analysis of Vasculature. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.00513"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"101626","DOI":"10.1016\/j.ijgc.2024.101626","article-title":"Probe-Based Confocal Laser Endomicroscopy Intra-Operative Evaluation in Ovarian Cancer: Definition of in Vivo Architectural Patterns to Determine Resection Strategies","volume":"35","author":"Spessotto","year":"2025","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9819","DOI":"10.1038\/s41598-017-10963-1","article-title":"Probe-Based Confocal Laser Endomicroscopy for in Vivo Evaluation of the Tumor Vasculature in Gastric and Rectal Carcinomas","volume":"7","author":"Spessotto","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1136\/gutjnl-2011-300695","article-title":"Local Barrier Dysfunction Identified by Confocal Laser Endomicroscopy Predicts Relapse in Inflammatory Bowel Disease","volume":"61","author":"Kiesslich","year":"2012","journal-title":"Gut"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"25600","DOI":"10.1038\/s41598-025-09680-x","article-title":"Disrupted Mucosal Vascular Barrier in Eosinophilic Esophagitis","volume":"15","author":"Lenti","year":"2025","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"26317745261436496","DOI":"10.1177\/26317745261436496","article-title":"Probing the Gut Barrier: Epithelial Permeability as a Dynamic Marker in Eosinophilic Gastroenteritis via pCLE","volume":"19","author":"Spessotto","year":"2026","journal-title":"Ther. Adv. Gastrointest. Endosc."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/s41575-023-00766-3","article-title":"Paracellular Permeability and Tight Junction Regulation in Gut Health and Disease","volume":"20","author":"Horowitz","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1136\/gutjnl-2018-317571","article-title":"Structural Weakening of the Colonic Mucus Barrier Is an Early Event in Ulcerative Colitis Pathogenesis","volume":"68","author":"Jabbar","year":"2019","journal-title":"Gut"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5853","DOI":"10.3168\/jds.2025-28138","article-title":"Synbiotics Regulate Gut Microbiota-Derived Indole-3-Acetic Acid Production to Modulate the Intestinal Barrier and Improve Antibiotic-Associated Diarrhea","volume":"109","author":"Shan","year":"2026","journal-title":"J. Dairy Sci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"eabo2794","DOI":"10.1126\/sciadv.abo2794","article-title":"Inhibition of Microbial Deconjugation of Micellar Bile Acids Protects against Intestinal Permeability and Liver Injury","volume":"8","author":"Li","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e13252","DOI":"10.1002\/smll.202513252","article-title":"Inulin-Butyrate Nanogel for Modulation of Gut Microbiome, Intestinal Barrier, and Regulatory T-Cells in Colitis","volume":"22","author":"Park","year":"2026","journal-title":"Small"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"119607","DOI":"10.1016\/j.foodres.2026.119607","article-title":"Anti-Inflammatory and Barrier-Protective Effects of Metabolites from Lactobacillus Co-Fermentation with Linoleic Acid and Human Fecal Microbiota","volume":"240","author":"Jin","year":"2026","journal-title":"Food Res. Int."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1053\/j.gastro.2021.06.025","article-title":"Interferon-Gamma-Producing CD8+ Tissue Resident Memory T Cells Are a Targetable Hallmark of Immune Checkpoint Inhibitor-Colitis","volume":"161","author":"Sasson","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1038\/s41591-024-02895-x","article-title":"Single-Cell Transcriptomic Analyses Reveal Distinct Immune Cell Contributions to Epithelial Barrier Dysfunction in Checkpoint Inhibitor Colitis","volume":"30","author":"Thomas","year":"2024","journal-title":"Nat. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1158\/2326-6066.CIR-22-0362","article-title":"Checkpoint Blockade-Induced Dermatitis and Colitis Are Dominated by Tissue-Resident Memory T Cells and Th1\/Tc1 Cytokines","volume":"10","author":"Reschke","year":"2022","journal-title":"Cancer Immunol. Res."},{"key":"ref_46","doi-asserted-by":"crossref","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":"ref_47","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1038\/s41586-023-06721-1","article-title":"Epithelial IFN\u03b3 Signalling and Compartmentalized Antigen Presentation Orchestrate Gut Immunity","volume":"623","author":"Malik","year":"2023","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"114287","DOI":"10.1016\/j.yexcr.2024.114287","article-title":"TIPE2 Aggravates Experimental Colitis and Disrupts Intestinal Epithelial Barrier Integrity by Activating JAK2\/STAT3\/SOCS3 Signal Pathway","volume":"443","author":"Zeng","year":"2024","journal-title":"Exp. Cell Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Drymel, B., Tomela, K., Galus, \u0141., Olejnik-Schmidt, A., Mackiewicz, J., Kaczmarek, M., Mackiewicz, A., and Schmidt, M. (2025). Characteristics of Intestinal Barrier State and Immunoglobulin-Bound Fraction of Stool Microbiota in Advanced Melanoma Patients Undergoing Anti-PD-1 Therapy. Int. J. Mol. Sci., 26.","DOI":"10.20944\/preprints202506.1274.v1"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1136\/gutjnl-2025-337780","article-title":"Targeting MLCK1 Uncouples Immune Checkpoint Inhibitor-Induced Colitis from Antitumour Immunity","volume":"75","author":"Xiong","year":"2026","journal-title":"Gut"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/s41416-020-0882-y","article-title":"Immune Checkpoint Inhibitor-Related Colitis Assessment and Prognosis: Can IBD Scoring Point the Way?","volume":"123","author":"Cheung","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e013823","DOI":"10.1136\/jitc-2025-013823","article-title":"Fecal Microbiota Transplantation Combined with Anti-PD-1 Therapy in Refractory Microsatellite-Stable Gastric Cancer: A Phase I Feasibility and Safety Study","volume":"14","author":"Zhang","year":"2026","journal-title":"J. Immunother. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1002\/jgh3.12531","article-title":"Calcineurin Inhibitors in Steroid and Anti-TNF-Alpha Refractory Immune Checkpoint Inhibitor Colitis","volume":"5","author":"Zhang","year":"2021","journal-title":"JGH Open"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/s12328-023-01887-7","article-title":"A Case of Refractory Immune Checkpoint Inhibitor-Induced Colitis Improved by the Treatment with Vedolizumab and Granulocyte-Monocyte Apheresis Combination Therapy","volume":"17","author":"Ishihara","year":"2024","journal-title":"Clin. J. Gastroenterol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1038\/s41586-019-1162-y","article-title":"Prophylactic TNF Blockade Uncouples Efficacy and Toxicity in Dual CTLA-4 and PD-1 Immunotherapy","volume":"569","author":"Minute","year":"2019","journal-title":"Nature"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1038\/s41591-018-0238-9","article-title":"Fecal Microbiota Transplantation for Refractory Immune Checkpoint Inhibitor-Associated Colitis","volume":"24","author":"Wang","year":"2018","journal-title":"Nat. Med."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1186\/s40425-018-0461-4","article-title":"Outcomes of Vedolizumab Therapy in Patients with Immune Checkpoint Inhibitor-Induced Colitis: A Multi-Center Study","volume":"6","author":"Ali","year":"2018","journal-title":"J. Immunother. Cancer"},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Huang, C., Li, M., Liu, B., Zhu, H., Dai, Q., Fan, X., Mehta, K., Huang, C., Neupane, P., and Wang, F. (2021). Relating Gut Microbiome and Its Modulating Factors to Immunotherapy in Solid Tumors: A Systematic Review. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.642110"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1038\/s41591-025-04183-8","article-title":"Fecal Microbiota Transplantation plus Immunotherapy in Metastatic Renal Cell Carcinoma: The Phase 1 PERFORM Trial","volume":"32","author":"Fernandes","year":"2026","journal-title":"Nat. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"118560","DOI":"10.1016\/j.biopha.2025.118560","article-title":"Microbiota-Derived Butyrate Potentiates MSLN CAR-T Cell Therapy by Metabolic Reprogramming and Extracellular Matrix Remodeling","volume":"192","author":"Chen","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Lin, A., Huang, L., Jiang, A., Zhu, L., Mou, W., Li, Y., Zhang, C., Liu, Z., Zhang, J., and Cheng, Q. (2025). Microbiota Boost Immunotherapy? A Meta-Analysis Dives into Fecal Microbiota Transplantation and Immune Checkpoint Inhibitors. BMC Med., 23.","DOI":"10.1186\/s12916-025-04183-y"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1053\/j.gastro.2025.04.025","article-title":"Pharmacomicrobiomics: The Role of the Gut Microbiome in Immunomodulation and Cancer Therapy","volume":"169","author":"Bolte","year":"2025","journal-title":"Gastroenterology"},{"key":"ref_63","doi-asserted-by":"crossref","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":"ref_64","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1007\/s00262-026-04480-2","article-title":"R-5780, a SagA-Engineered Lactococcus lactis, Is a Safe Oral Synthetic-Biology Microbial Therapy That Potentiates PD-1 Blockade","volume":"75","author":"Fukuhara","year":"2026","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e014702","DOI":"10.1136\/jitc-2025-014702","article-title":"Phase I Trial of CJRB-101 plus Pembrolizumab in Patients with Metastatic Non-Small Cell Lung Cancer, Head and Neck Squamous Cell Carcinoma and Melanoma","volume":"14","author":"Lee","year":"2026","journal-title":"J. Immunother. Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1038\/nature12721","article-title":"Commensal Microbe-Derived Butyrate Induces the Differentiation of Colonic Regulatory T Cells","volume":"504","author":"Furusawa","year":"2013","journal-title":"Nature"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"112135","DOI":"10.1016\/j.celrep.2023.112135","article-title":"Dietary Tryptophan Deficiency Promotes Gut ROR\u03b3t+ Treg Cells at the Expense of Gata3+ Treg Cells and Alters Commensal Microbiota Metabolism","volume":"42","author":"Rankin","year":"2023","journal-title":"Cell Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/nature12726","article-title":"Metabolites Produced by Commensal Bacteria Promote Peripheral Regulatory T-Cell Generation","volume":"504","author":"Arpaia","year":"2013","journal-title":"Nature"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Malczewski, A.B., Ketheesan, N., Coward, J.I.G., and Navarro, S. (2021). Enhancing Checkpoint Inhibitor Therapy in Solid Tissue Cancers: The Role of Diet, the Microbiome & Microbiome-Derived Metabolites. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.624434"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1136\/gutjnl-2017-315136","article-title":"Randomised Placebo-Controlled Trial of Dietary Glutamine Supplements for Postinfectious Irritable Bowel Syndrome","volume":"68","author":"Zhou","year":"2019","journal-title":"Gut"},{"key":"ref_71","doi-asserted-by":"crossref","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":"ref_72","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1080\/1750743X.2026.2648431","article-title":"Harnessing the Gut Microbiota in Extra-Intestinal Cancers: From Causal Evidence to Immunotherapy Strategies","volume":"18","author":"Mattavelli","year":"2026","journal-title":"Immunotherapy"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1053\/j.gastro.2020.08.005","article-title":"Increased Intestinal Permeability Is Associated with Later Development of Crohn\u2019s Disease","volume":"159","author":"Turpin","year":"2020","journal-title":"Gastroenterology"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1136\/gutjnl-2019-318427","article-title":"Leaky Gut: Mechanisms, Measurement and Clinical Implications in Humans","volume":"68","author":"Camilleri","year":"2019","journal-title":"Gut"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"G11","DOI":"10.1152\/ajpgi.00113.2021","article-title":"Biomarkers for Assessment of Intestinal Permeability in Clinical Practice","volume":"321","author":"Seethaler","year":"2021","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1111\/apt.12194","article-title":"Serum I-FABP as Marker for Enterocyte Damage in Coeliac Disease and Its Relation to Villous Atrophy and Circulating Autoantibodies","volume":"37","author":"Adriaanse","year":"2013","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/j.cgh.2017.12.024","article-title":"Association Between Low Plasma Level of Citrulline Before Allogeneic Hematopoietic Cell Transplantation and Severe Gastrointestinal Graft vs Host Disease","volume":"16","author":"Hueso","year":"2018","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"8452","DOI":"10.3748\/wjg.v23.i48.8452","article-title":"Human Small Intestine Is Capable of Restoring Barrier Function after Short Ischemic Periods","volume":"23","author":"Schellekens","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.14309\/ajg.0000000000000827","article-title":"Evidence of Duodenal Epithelial Barrier Impairment and Increased Pyroptosis in Patients with Functional Dyspepsia on Confocal Laser Endomicroscopy and \u201cEx Vivo\u201d Mucosa Analysis","volume":"115","author":"Nojkov","year":"2020","journal-title":"Am. J. Gastroenterol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1053\/j.gastro.2024.07.004","article-title":"Molecular Mechanisms Underlying Loss of Vascular and Epithelial Integrity in Irritable Bowel Syndrome","volume":"167","author":"Barbaro","year":"2024","journal-title":"Gastroenterology"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1055\/s-0029-1243951","article-title":"Interobserver Agreement and Accuracy among International Experts with Probe-Based Confocal Laser Endomicroscopy in Predicting Colorectal Neoplasia","volume":"42","author":"Gomez","year":"2010","journal-title":"Endoscopy"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1055\/s-0030-1256767","article-title":"New Classification for Probe-Based Confocal Laser Endomicroscopy in the Colon","volume":"43","author":"Kuiper","year":"2011","journal-title":"Endoscopy"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"645173","DOI":"10.1155\/2012\/645173","article-title":"Probe-Based Confocal Laser Endomicroscopy Evaluation of Colon Preneoplastic Lesions, with Particular Attention to the Aberrant Crypt Foci, and Comparative Assessment with Histological Features Obtained by Conventional Endoscopy","volume":"2012","author":"Mascolo","year":"2012","journal-title":"Gastroenterol. Res. Pract."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1111\/jgh.14471","article-title":"Role of Probe-Based Confocal Laser Endomicroscopy-Targeted Biopsy in the Molecular and Histopathological Study of Gastric Cancer","volume":"34","author":"Park","year":"2019","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1177\/2050640614566066","article-title":"Use of Probe-Based Confocal Laser Endomicroscopy (pCLE) in Gastrointestinal Applications. A Consensus Report Based on Clinical Evidence","volume":"3","author":"Wang","year":"2015","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.gie.2016.05.011","article-title":"Lower Dose of Fluorescein Sodium Is More Suitable for Confocal Laser Endomicroscopy: A Feasibility Study","volume":"84","author":"Zhang","year":"2016","journal-title":"Gastrointest. Endosc."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"21053","DOI":"10.1038\/s41598-021-00550-w","article-title":"pCLE Highlights Distinctive Vascular Patterns in Early Gastric Cancer and in Gastric Diseases with High Risk of Malignant Complications","volume":"11","author":"Fornasarig","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"3512","DOI":"10.1245\/s10434-025-19055-1","article-title":"Probe-Based Confocal Laser Endomicroscopy in Gynecologic Surgical Oncology: Intraoperative Insights to Guide Surgical Resection","volume":"33","author":"Ferla","year":"2026","journal-title":"Ann. Surg. Oncol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1093\/ibd\/izac233","article-title":"Computer-Aided Imaging Analysis of Probe-Based Confocal Laser Endomicroscopy with Molecular Labeling and Gene Expression Identifies Markers of Response to Biological Therapy in IBD Patients: The Endo-Omics Study","volume":"29","author":"Iacucci","year":"2023","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"G424","DOI":"10.1152\/ajpgi.00447.2025","article-title":"Tools and Advanced Imaging Technologies for Assessing Intestinal Epithelial Barrier Integrity: A Systematic Review","volume":"330","author":"Vieujean","year":"2026","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1053\/j.gastro.2022.10.014","article-title":"Intestinal Barrier Healing Is Superior to Endoscopic and Histologic Remission for Predicting Major Adverse Outcomes in Inflammatory Bowel Disease: The Prospective ERIca Trial","volume":"164","author":"Rath","year":"2023","journal-title":"Gastroenterology"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/18\/3086\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T16:10:54Z","timestamp":1790007054000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/18\/3086"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,20]]},"references-count":91,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["nu18183086"],"URL":"https:\/\/doi.org\/10.3390\/nu18183086","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,20]]}}}