Microbial signals in primary and metastatic brain tumors
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.
Authors
- Diana D. Shamsutdinova (ORCID: https://orcid.org/0000-0003-1057-1731)
- Longfei Huo
- Lihong Long
- Natalie W. Fowlkes (ORCID: https://orcid.org/0000-0002-7711-6031)
- Ivonne I. Flores (ORCID: https://orcid.org/0009-0009-9905-1644)
- Florentia Dimitriou (ORCID: https://orcid.org/0000-0003-4529-3372)
- Rene N. Rico
- Malgorzata Anna Zal (ORCID: https://orcid.org/0000-0002-1015-3954)
- Pravesh Gupta (ORCID: https://orcid.org/0000-0002-1643-8950)
- Priscilla Kaliopi Brastianos (ORCID: https://orcid.org/0000-0003-4470-8425)
- Rebecca Soto
- Davis R. Ingram (ORCID: https://orcid.org/0000-0001-5967-1501)
- Nadim J. Ajami (ORCID: https://orcid.org/0000-0002-3808-8576)
- Matthew C. Wong (ORCID: https://orcid.org/0000-0002-6317-2526)
- Lisa Norberg (ORCID: https://orcid.org/0009-0007-5741-8773)
- Eiko Hayase (ORCID: https://orcid.org/0000-0002-4824-8844)
- Robert R. Jenq (ORCID: https://orcid.org/0000-0002-5434-439X)
- Frederick F. Lang (ORCID: https://orcid.org/0000-0003-3747-873X)
- Samuel W. Andrewes
- Khalida Wani (ORCID: https://orcid.org/0000-0002-2383-3908)
- Stephanie L. Jenkins (ORCID: https://orcid.org/0009-0004-9194-0205)
- Jennifer Ann Wargo (ORCID: https://orcid.org/0000-0003-3438-7576)
- Vinay K. Puduvalli (ORCID: https://orcid.org/0000-0001-8396-9500)
- Christopher D. Johnston (ORCID: https://orcid.org/0000-0002-6765-2383)
- Pavel S. Pichardo‐Rojas (ORCID: https://orcid.org/0000-0002-0804-2825)
- Nitin Tandon (ORCID: https://orcid.org/0000-0002-2752-2365)
- Susan Bullman (ORCID: https://orcid.org/0000-0002-7713-0810)
- Brenda Melendez (ORCID: https://orcid.org/0000-0001-8789-6791)
- Abderrahman Day (ORCID: https://orcid.org/0000-0002-3338-5088)
- Michael A. Davies (ORCID: https://orcid.org/0000-0002-0977-0912)
- Phoebe Doss
- Sherise Desiree Ferguson (ORCID: https://orcid.org/0000-0002-6344-0615)
- Alexander J. Lazar (ORCID: https://orcid.org/0000-0002-6395-4499)
- Sharyl J. Nass (ORCID: https://orcid.org/0000-0001-5874-5337)
- Lauren McDaniel
- Golnaz Morad (ORCID: https://orcid.org/0000-0002-9460-618X)
- Manoj Chelvanambi (ORCID: https://orcid.org/0000-0003-2130-3118)
- Jing Yang (ORCID: https://orcid.org/0000-0001-5143-160X)
- Jillian Losh (ORCID: https://orcid.org/0000-0003-4648-6512)
- Mona M. Ahmed (ORCID: https://orcid.org/0000-0003-2149-5439)
- Mohamed A. Jamal (ORCID: https://orcid.org/0000-0003-3404-2535)
- Joy Gumin
- Ashish Damania (ORCID: https://orcid.org/0009-0001-3158-2846)
- Sarah B. Johnson (ORCID: https://orcid.org/0000-0001-8936-0958)
- Mahesh Bekal (ORCID: https://orcid.org/0000-0002-6329-0477)
- Krishna Bhat (ORCID: https://orcid.org/0000-0002-2020-8509)
- Candelaria Gomez‐Manzano (ORCID: https://orcid.org/0000-0002-1259-2133)
- Leomar Y. Ballester (ORCID: https://orcid.org/0000-0002-6854-6830)
- Antonio Dono (ORCID: https://orcid.org/0000-0002-8041-8399)
- Chia‐Chi Chang (ORCID: https://orcid.org/0000-0003-0050-1705)
- Eric A. Goethe (ORCID: https://orcid.org/0000-0002-4151-2059)
- Brittany C. Parker Kerrigan (ORCID: https://orcid.org/0009-0005-9268-0342)
- Shivangi Oberai (ORCID: https://orcid.org/0009-0009-3480-2101)
- Pranoti Sahasrabhojane
- Grace Bradley (ORCID: https://orcid.org/0000-0002-9008-8696)
- Chetna Wathoo
- Yoshua Esquenazi (ORCID: https://orcid.org/0000-0002-9757-1453)
- Christine B. Peterson (ORCID: https://orcid.org/0000-0003-3316-0468)
- Dorte Nielsen (ORCID: https://orcid.org/0000-0002-8766-8729)
- Rossana N. Lazcano Segura
- Yasmine Hoballah
- Fabiana J. Veguilla
- Bharat Singh (ORCID: https://orcid.org/0000-0001-9168-4521)
- Jason T. Huse (ORCID: https://orcid.org/0000-0003-4514-0640)
- Jiyong Liang
- Kaitlyn N. Lewis
Institutions
- Broad Institute (US)
- Houston Methodist (US)
- The University of Texas MD Anderson Cancer Center (US)
- Baylor College of Medicine (US)
- Massachusetts General Hospital (US)
- City of Hope (US)
- Dana-Farber Cancer Institute (US)
- Mayo Clinic in Arizona (US)
- Massachusetts Institute of Technology (US)
- The University of Texas Southwestern Medical Center (US)
- The University of Texas Health Science Center at Houston (US)
Publication Details
- Journal
- Nature Medicine
- Published
- 2025-11-01
- DOI
- https://doi.org/10.1038/s41591-025-03957-4
- Citations
- 3
- Primary Topic
- Cancer Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 3.70