Gut microbiota composition and tumor immune features in meningioma patients

Meningiomas are prevalent intracranial tumors with poorly understood extraneural drivers. While the gut-brain axis influences neuro-oncogenesis, meningioma-specific gut microbiome alterations and their clinical implications remain uncharacterized. This study integrated 16S rRNA sequencing of fecal samples from 15 treatment-naïve WHO grade I meningioma patients (MPs) and 15 healthy controls (HCs) with immunohistochemical profiling of tumor immune infiltrates (MPO⁺ neutrophils, CD68⁺ macrophages, CD3⁺ T cells). Compared with HCs, MPs exhibited significantly reduced alpha diversity (Shannon index, <i>P</i> = 0.026) and distinct beta diversity (permutational multivariate analysis of variance, <i>P</i> < 0.0009). Taxonomic analysis revealed enrichment of <i>Proteobacteria</i> (28.82% vs. 2.46%, <i>P</i> = 0.001), specifically <i>Escherichia_Shigella</i> at the genus level (25.95% vs. 1.61%, <i>P</i> = 0.008), along with depletion of <i>Bacteroidaceae</i> and <i>Ruminococcaceae</i>. LEfSe identified <i>Escherichia_Shigella</i> as the top meningioma-enriched biomarker. In diagnostic modeling, <i>Escherichia_Shigella</i> achieved an area under the receiver operating characteristic curve of 95.11% (95% CI: 86.91%-100%) for WHO grade I meningioma detection. Critically, <i>Escherichia_Shigella</i> abundance positively correlated with intratumoral MPO⁺, CD68⁺, and CD3⁺ cell densities (all <i>P</i> < 0.05), whereas <i>Ruminococcaceae</i> showed inverse correlations. The 16S rRNA sequencing data are publicly available in the GSA database under accession number CRA027974. This study provides the first evidence of gut dysbiosis in grade I meningioma, characterized by <i>Escherichia_Shigella</i> dominance and depletion of immunomodulatory commensals. This signature correlates with increased immune infiltration and holds promise as a novel biomarker.<h4>Importance</h4>Detailed exploration of host-microbe interactions can be worthwhile. Gut dysbiosis has been implicated in neuroinflammation, blood-brain barrier disruption, and oncogenesis in multiple cancer types, including gliomas. However, the gut microbiota composition and metabolic characteristics in patients with meningioma have not been previously reported. To address these critical knowledge gaps, we conducted a case-control study integrating 16S rRNA sequencing, clinical phenotyping, and immunohistochemical profiling. Our study revealed significant alterations in the gut microbiota of MPs, characterized by reduced alpha diversity, enrichment of <i>Proteobacteria</i>, and depletion of beneficial taxa, including <i>Bacteroidaceae</i> and <i>Ruminococcaceae</i>. Critically, we identified <i>Escherichia_Shigella</i> as a potential diagnostic biomarker and demonstrated strong correlations between elevated <i>Escherichia_Shigella</i>/Enterobacteriaceae abundance and increased intratumoral infiltration of MPO⁺ neutrophils, CD68⁺ macrophages, and CD3⁺ T cells. These findings are the first evidence that gut microbiome dysbiosis is closely associated with meningioma inflammation.