{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T13:29:36Z","timestamp":1789046976728,"version":"build-2803163510"},"reference-count":101,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Glioblastoma (GBM) is the most aggressive primary brain tumor in adults and remains difficult to treat because of diffuse invasion, immunosuppression, metabolic adaptability, and therapy resistance. This review evaluates how gut microbiota and microbiota\u2010associated neuroinflammatory signaling may contribute to GBM biology and therapeutic response.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>We synthesized mechanistic, preclinical, translational, and emerging clinical evidence on microbiota\u2010neuroinflammation interactions in GBM. The review focused on gut\u2010brain axis pathways, microbial metabolites, blood\u2010brain barrier (BBB) regulation, glial and myeloid immune activity, tumor\u2010associated microbial signatures, microbial peptide\u2010HLA presentation, and microbiome\u2010informed biomarker or therapeutic strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Finding<\/jats:title>\n                    <jats:p>Current evidence suggests that microbiota\u2010related signals may influence GBM through systemic immune modulation, short\u2010chain fatty acids, tryptophan\u2010derived metabolites, polyamines, BBB effects, and altered microglial and tumor\u2010associated myeloid cell function. Polyamine metabolism may sustain myeloid\u2010cell\u2010mediated immunosuppression in the acidic GBM tumor microenvironment, whereas microglial GLUT5\u2010dependent fructose metabolism may limit inflammatory antigen presentation and adaptive antitumor immunity. Sequencing\u2010based studies have reported bacterial and fungal nucleic acid signatures in brain tumor specimens, but these findings require careful interpretation because of low biomass, contamination risk, and methodological variability. Preclinical models further indicate that microbiome modulation can alter inflammatory tone, tumor growth, immune\u2010cell infiltration, and response to immune checkpoint blockade.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Microbiota\u2010regulated neuroinflammation is a biologically plausible contributor to GBM progression, immune suppression, and treatment resistance. However, most evidence remains preclinical or early translational. Well\u2010controlled, spatially resolved, multi\u2010omic studies are required before microbiome\u2010based biomarkers or interventions can be clinically implemented for patient stratification and future precision clinical neuro\u2010oncology applications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71648","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T08:10:55Z","timestamp":1785917455000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microbiota\u2013Neuroinflammation Crosstalk in Primary Brain Tumors: Focus on Glioblastoma"],"prefix":"10.1002","volume":"16","author":[{"given":"Tareq Nayef","family":"AlRamadneh","sequence":"first","affiliation":[{"name":"Faculty of Allied Medical Sciences, Hourani Center For Applied Scientific Research Al\u2010Ahliyya Amman University  Amman Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renuka 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