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Microbial signals in primary and metastatic brain tumors


ABSTRACT: Gliomas and brain metastases (BrM) are associated with poor prognosis, necessitating a deeper understanding of brain tumor biology and the development of effective therapeutic strategies. While our group and others have demonstrated microbial presence in various tumors, recent controversies regarding cancer-type-specific intra-tumoral 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 BrM samples and 75 non-cancerous or tumor-adjacent tissues. Using stringent fluorescent in situ hybridization, immunohistochemistry, and high-resolution spatial imaging, we detected intracellular bacterial 16S rRNA and lipopolysaccharides in both glioma and BrM samples, localized to tumor, immune, and stromal cells. Custom 16S and metagenomic sequencing workflows identified taxa associated with intra-tumoral 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 anti-microbial and immunometabolic signatures at regional, neighborhood, and cellular levels. Furthermore, intra-tumoral 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE305267 | GEO | 2025/08/12

REPOSITORIES: GEO

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