P13.11.B INTRATUMORAL LACTOBACILLUS INTESTINALIS-DERIVED METABOLITE ATTENUATES MENINGIOMA MALIGNANCY BY SUPPRESSING ONCOGENIC PATHWAYS AND REPROGRAMMING THE IMMUNE MICROENVIRONMENT

Abstract BACKGROUND Emerging evidence implicates intratumoral microbiota in cancer progression, yet their role in meningiomas—the most common primary intracranial tumors—remains unexplored. This study investigates the immunomodulatory and antitumor effects of intratumoral Lactobacillus intestinalis (L. intestinalis), a commensal gut bacterium, and its metabolite indole-3-lactic acid (ILA) and naicin in meningioma. METHODS We analyzed 80 meningioma tissues (44 benign, 36 non-benign) using 16S rRNA sequencing, validated bacterial presence via fluorescence in situ hybridization (FISH) and transmission electron microscopy (TEM), and isolated Lactobacillus intestinalis. Dual FISH/immunofluorescence (IF) co-localization analysis was performed using a Lactobacillus intestinalis-specific FISH probe combined with immune cell markers (CD8, iNOS, CD163) to map bacterial spatial distribution. Non-targeted metabolomics identified key metabolites (indole-3-lactic acid [ILA], niacin). Functional assays included cell proliferation/scratch/Transwell migration tests, RNA sequencing, and PBMC/THP-1-derived macrophage co-culture systems to evaluate tumor-immune crosstalk. RESULTS Meningiomas harbored diverse intratumoral microbiota dominated by Firmicutes and Bacteroidota, with distinct community structures between benign and non-benign groups. Non-benign tumors exhibited reduced Lactobacillus intestinalis (L. intestinalis) abundance. Dual FISH/IF confirmed L. intestinalis co-localization with cytotoxic T cells (CD8+) and macrophages (CD80+/CD163+) in tumor tissues. L. intestinalis metabolite suppressed IOMM-Lee cell proliferation and migration. In PBMC co-culture systems mimicking human TME, ILA /niacin skewed macrophages toward M1 polarization and transcriptomics revealed ILA+TME mediated suppression of cell proliferation, DNA damage repair, and migration-related pathways, coupled with activation of tumor-suppressive stress responses. CONCLUSION This study identifies L. intestinalis-derived ILA as a microbial effector that reprograms the meningioma immune microenvironment and directly suppresses oncogenic signaling. Our findings highlight the therapeutic potential of targeting intratumoral microbiota-metabolite axes in central nervous system tumors.