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Resistance to these therapies necessitates innovative approaches, such as immune checkpoint inhibitors (ICIs) targeting cytotoxic T\u2010lymphocyte\u2010associated protein 4 (CTLA\u20104), programmed cell death protein 1 (PD\u20101), and programmed death ligand 1 (PD\u2010L1) to enhance T\u2010cell\u2010mediated tumor destruction. However, clinical trials have shown limited ICI efficacy in GB due to its immunosuppressive microenvironment and the blood\u2013brain tumor barrier (BBTB), which impairs drug delivery. Emerging evidence highlights the gut microbiota as a pivotal modulator of ICI response, enhancing CD8\n                    <jats:sup>+<\/jats:sup>\n                    and CD4\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell function, antigen presentation, and immune modulation via the gut\u2010brain axis in cancers. In addition, studies showed that gut\u2010derived metabolites, including short\u2010chain fatty acids, modulate immune responses and support blood\u2013brain barrier integrity by regulating inflammatory signaling and tight junction proteins. Future GB research should prioritize clinical trials, mechanistic studies, and interventional strategies like fecal microbiota transplantation and probiotics to enhance ICI efficacy.\n                  <\/jats:p>","DOI":"10.1002\/biof.70077","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T12:39:33Z","timestamp":1770035973000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Gut Microbiome Strategies for Enhancing\n                    <scp>ICI<\/scp>\n                    Delivery Across the\n                    <scp>BBB<\/scp>\n                    in Glioblastoma"],"prefix":"10.1002","volume":"52","author":[{"given":"Sama","family":"Barati","sequence":"first","affiliation":[{"name":"Student Research Committee Mashhad University of Medical Sciences  Mashhad 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