Specific Intratumoral Microbiome Signatures in Human Glioblastoma and Meningioma: Evidence for a Gut–Brain Microbial Axis

Brain tumors (BTs), including glioblastoma (GBM) and meningioma (MGM), contribute significantly to the global cancer burden. The microbiome has been implicated in carcinogenesis, yet its role in BTs remains underexplored. We performed 16S rRNA gene sequencing of the gut microbiota (GM) and intratumoral microbiome (ItM) from fresh tissue samples of 9 patients with GBM and 18 with MGM. 12 age- and sex-matched healthy controls (HCs) were also enrolled. GM profiling revealed reduced alpha diversity and distinct microbial communities in BT patients versus HCs. Notably, Verrucomicrobiota and Synergistaceae were enriched, while Lachnospiraceae, Peptostreptococcaceae, and <i>Muribacter</i> spp. were depleted. GBM patients showed reductions in Peptostreptococcaceae and the <i>Eubacterium hallii</i> group, while MGM patients had increased <i>Synergistia</i> and <i>Erysipelatoclostridium</i>. Compared with MGM, GBM patients were enriched in Peptostreptococcales-Tissierellales, <i>Coprobacillus</i>, and <i>Peptoniphilus</i> but depleted in <i>Weissella</i>. Venn analysis revealed 176 genera shared across groups with unique taxa distinguishing tumor patients and HCs. ItM profiling revealed enrichment of Proteobacteria, Actinomycetota, and Campylobacterota in GBM, while MGM contained higher levels of Bacillota and Bacteroidota. GBM tissues harbored <i>Burkholderia-Caballeronia-Paraburkholderia</i>, <i>Helicobacter</i>, and <i>Leifsonia</i>, whereas MGM tissues were dominated by <i>Bacteroides</i> and <i>Blautia</i>. Notably, stool and tumor samples shared 91 genera in GBM and 105 in MGM. This study provides novel insights by (i) characterizing ItM from fresh samples, (ii) comparing ItM profiles of GBM and MGM, (iii) linking GM and ItM within the same patients, and (iv) suggesting potential clinical implications for BT management.