Faculty, Staff and Student Publications

Language

English

Publication Date

11-1-2025

Journal

Nature Medicine

DOI

10.1038/s41591-025-03957-4

PMID

41238915

PMCID

PMC12618227

PubMedCentral® Posted Date

11-14-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Gliomas and brain metastases are associated with poor prognosis, necessitating a deeper understanding of brain tumor biology and the development of effective therapeutic strategies. Although our group and others have demonstrated microbial presence in various tumors, recent controversies regarding cancer-type-specific intratumoral microbiota emphasize the importance of rigorous, orthogonal validation. This prospective, multi-institutional study included a total of 243 samples from 221 patients, comprising 168 glioma and brain metastases samples and 75 non-cancerous or tumor-adjacent tissues. Using stringent fluorescence in situ hybridization, immunohistochemistry and high-resolution spatial imaging, we detected intracellular bacterial 16S rRNA and lipopolysaccharides in both glioma and brain metastases samples, localized to tumor, immune and stromal cells. Custom 16S and metagenomic sequencing workflows identified taxa associated with intratumoral bacterial signals in the tumor microenvironment; however, standard culture methods did not yield readily cultivable microbiota. Spatial analyses revealed significant correlations between bacterial 16S signals and antimicrobial and immunometabolic signatures at regional, neighborhood and cellular levels. Furthermore, intratumoral 16S bacterial signals showed sequence overlap with matched oral and gut microbiota, suggesting a possible connection with distant communities. Together, these findings introduce microbial elements as a component of the brain tumor microenvironment and lay the foundation for future mechanistic and translational studies.

Keywords

Humans, Brain Neoplasms, RNA, Ribosomal, 16S, Tumor Microenvironment, Female, Glioma, Male, Prospective Studies, Middle Aged, Microbiota, In Situ Hybridization, Fluorescence, Aged, Adult, Bacteria, CNS cancer, Bacterial host response

Published Open-Access

yes

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