Multi-omics analysis reveals the interplay between intratumoral bacteria and glioma

Emerging evidence highlights the potential impact of intratumoral microbiota on cancer. However, the microbial composition and function in glioma remains elusive. Consequently, our study aimed to investigate the microbial commun ity composition in glioma tissues and elucidate its role in glioma development. We parallelly performed microbial profiling, transcriptome sequencing, and metabolomics detection on tumor and adjacent normal brain tissues obtained from 50 glioma patients. We employed immunohistochemistry, multicolor immunofluorescence, and fluorescence in situ hybridization (FISH) staining to observe the presence and location of bacteria. Furthermore, an animal model was employed to validate the impact of key bacteria on glioma development. Six genera were found to be significantly enriched in glioma tissues compared to adjacent normal brain tissues, including Fusobacterium, Longibacu lum, Intestinimonas, Pasteurella, Limosilactobacillus, and Arthrobacter. Both bacterial RNA and lipopolysaccharides (LPS) were observed in glioma tissues. Integrated microbiomics, transcriptomics, and metabolomics revealed that genes associated with intratumoral microbes were enriched in multiple synapse-associated pathways and that metabolites associated with intratumoral microbes were (R)-N-methylsalsolinol, N-acetylaspartylglu tamic acid, and N-acetyl- L-aspar tic acid. Further mediation analysis suggested that the intratumoral microbiome may affect the expression of neuron-related genes through bacteria-associated metabolites. In addition, both in vivo and in vitro models of glioma show that Fusobacterium nucleatum promotes glioma proliferation and upregulates CCL2, CXCL1, and CXCL2 levels. Our findings shed light on the intricate interplay between intratumoral bacteria and glioma.