Abstract

Abstract Background: The role of microbiome in different steps of tumor development and progression has been shown across various tumor types. However, the contribution of microbiome to brain tumors is yet to be understood. A crosstalk between the gut and oral microbiota and the brain microenvironment has been demonstrated in the context of neurological and neurodegenerative diseases. We hypothesize that distinct gut and oral microbial signatures are associated with primary and metastatic brain tumors. Methods: Matched stool, saliva, and buccal swab samples were collected prospectively from patients with primary or metastatic brain tumors who underwent surgical tumor resection at the University of Texas MD Anderson Cancer Center. Samples were collected using the OMNIgene microbiome collection and stabilization kits (DNAgenotek, Kit Number OM-200, OMR-120, and OM-505 for stool, buccal swab, and saliva, respectively). Samples were then processed, aliquoted, and stored at -80 C. Samples from 10 patients for each disease type were sequenced via metagenomic shotgun sequencing. Taxonomic profiling was conducted through MetaPhlAn and Virmap, for bacterial and viral taxa, respectively. Beta diversity was analyzed using Bray-Curtis and UniFrac analyses. Biom files were further analyzed to identify the signatures associated with each disease type, using the Phyloseq and Microbiome packages in R and heatmaps were generated using the Pheatmap package. Results: Microbiome beta diversity analysis demonstrated distinct clustering of stool, saliva, and buccal swab samples in both primary and metastatic brain tumor patients, which confirmed high sample quality and lack of cross-contamination between buccal swab and oral samples during sample collection. Analysis of oral microbiome samples demonstrated distinct bacterial and viral signatures that were enriched in metastatic brain tumors in comparison to primary brain tumors. In contrast, the composition of gut microbial taxa was comparable between metastatic and primary brain tumors and demonstrated enrichment in Bacteroides and Microviridae families. Conclusion: Our analysis of gut and oral microbiome in patients with primary and metastatic brain tumors suggest that distinct bacterial and viral taxa within the oral microbiome are enriched in metastatic brain tumors. We are in the process of expanding our clinical cohort to further validate these findings. Moreover, mechanistic studies are ongoing to understand the contribution of microbial signatures to the development and progression of metastatic and primary tumors. (These studies were supported by the National Institute of Health (F32CA260769) and the Glioblastoma Moonshot Program at the MD Anderson Cancer Center.) Citation Format: Golnaz Morad, Matthew Lastrapes, Matthew Wong, Pranoti Sahasrabhojane, Sherise Ferguson, Nadim Ajami, Jennifer Wargo. Distinct oral microbial signatures are associated with primary and metastatic brain tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3045.

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