Characterization of the tumor microbiome of brain metastases and glioblastoma reveals tumor-type-specific and location-specific microbial signatures

Elinor Gigi; Nancy Gavert; Lilach Raijman-Nagar; Yaara Zwang; Hofit Zemach; Ilana Livyatan; Adva Levy-Barda; Yossi Laviv; Andrew A. Kanner; Alexandra Amiel; Tali Siegal; Anca Leibovici; Inna Selezen; Omar Badran; Yaniv Zohar; Esraa Safadi; Lyndsey L. Prather; Cassandra R. Helfer; Patricia Castro; Iris Barshack; Tali Dadosh; Smadar Levin-Zaidman; Inna Goliand; Ofra Golani; Suzana Horn; Jacob J. Mandel; Noam Shental; Ayelet Shai; Shlomit Yust-Katz; Ravid Straussman

doi:10.1038/s43018-025-01073-3

Characterization of the tumor microbiome of brain metastases and glioblastoma reveals tumor-type-specific and location-specific microbial signatures

Elinor Gigi
, Nancy Gavert
, Lilach Raijman-Nagar
, Yaara Zwang
, Hofit Zemach
, Ilana Livyatan
, Adva Levy-Barda
, Yossi Laviv
, Andrew A. Kanner
, Alexandra Amiel
, Tali Siegal
, Anca Leibovici
, Inna Selezen
, Omar Badran
, Yaniv Zohar
, Esraa Safadi
, Lyndsey L. Prather
, Cassandra R. Helfer
, Patricia Castro
, Iris Barshack

Tali Dadosh, Smadar Levin-Zaidman, Inna Goliand, Ofra Golani, Suzana Horn, Jacob J. Mandel, Noam Shental, Ayelet Shai, Shlomit Yust-Katz, Ravid Straussman^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

Brain tumors, including glioblastoma multiforme (GBM) and brain metastases, present a notable clinical challenge. Recent research highlights the presence of intratumor bacteria across many tumor types, yet the microbiome of brain tumors remains largely underexplored. Here we show that the microbiome of 322 brain tumors differs markedly by tumor type and location. Using multiple approaches to visualize, culture and sequence bacterial communities, we found that brain metastases harbor higher bacterial richness and diversity than GBM, with distinct microbial compositions. Moreover, metastases in posterior brain regions exhibited greater diversity than those in anterior regions. Pathway analysis revealed enrichment of bacterial metabolic pathways associated with tumor spread and metastasis in brain metastases while GBM was enriched with pathways supporting alternative phosphorus use. These findings provide valuable insights into the microbial landscape of brain tumors, highlighting tumor-type-specific and location-specific variation and suggesting potential roles for bacteria in brain tumor biology.

Original language	English
Pages (from-to)	1761-1776
Number of pages	16
Journal	Nature Cancer
Volume	6
Issue number	11
DOIs	https://doi.org/10.1038/s43018-025-01073-3
Publication status	Published Online - 14 Nov 2025

Funding

We thank the participants and their families for their contribution to this research. We also thank members of the R.S. lab for their support. R.S. is supported by the Israel Cancer Research Fund (project grant no. 22-109-PG), The Mark Foundation for Cancer Research, the Israel Science Foundation (grant no. 2927/21), the European Research Council (European Union’s Horizon 2020 research and innovation program, grant agreement no. 818086), the Fabrikant–Morse Families Research Fund for Humanity, the Knell Family Center for Microbiology, the Moross Integrated Cancer Center, the Dr. Dvora and Haim Teitelbaum Endowment Fund and the Elsie and Marvin Dekelboum Family Foundation.

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

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10.1038/s43018-025-01073-3

Cite this

Gigi, E., Gavert, N., Raijman-Nagar, L., Zwang, Y., Zemach, H., Livyatan, I., Levy-Barda, A., Laviv, Y., Kanner, A. A., Amiel, A., Siegal, T., Leibovici, A., Selezen, I., Badran, O., Zohar, Y., Safadi, E., Prather, L. L., Helfer, C. R., Castro, P., ... Straussman, R. (2025). Characterization of the tumor microbiome of brain metastases and glioblastoma reveals tumor-type-specific and location-specific microbial signatures. Nature Cancer, 6(11), 1761-1776. Advance online publication. https://doi.org/10.1038/s43018-025-01073-3

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title = "Characterization of the tumor microbiome of brain metastases and glioblastoma reveals tumor-type-specific and location-specific microbial signatures",

abstract = "Brain tumors, including glioblastoma multiforme (GBM) and brain metastases, present a notable clinical challenge. Recent research highlights the presence of intratumor bacteria across many tumor types, yet the microbiome of brain tumors remains largely underexplored. Here we show that the microbiome of 322 brain tumors differs markedly by tumor type and location. Using multiple approaches to visualize, culture and sequence bacterial communities, we found that brain metastases harbor higher bacterial richness and diversity than GBM, with distinct microbial compositions. Moreover, metastases in posterior brain regions exhibited greater diversity than those in anterior regions. Pathway analysis revealed enrichment of bacterial metabolic pathways associated with tumor spread and metastasis in brain metastases while GBM was enriched with pathways supporting alternative phosphorus use. These findings provide valuable insights into the microbial landscape of brain tumors, highlighting tumor-type-specific and location-specific variation and suggesting potential roles for bacteria in brain tumor biology.",

author = "Elinor Gigi and Nancy Gavert and Lilach Raijman-Nagar and Yaara Zwang and Hofit Zemach and Ilana Livyatan and Adva Levy-Barda and Yossi Laviv and Kanner, \{Andrew A.\} and Alexandra Amiel and Tali Siegal and Anca Leibovici and Inna Selezen and Omar Badran and Yaniv Zohar and Esraa Safadi and Prather, \{Lyndsey L.\} and Helfer, \{Cassandra R.\} and Patricia Castro and Iris Barshack and Tali Dadosh and Smadar Levin-Zaidman and Inna Goliand and Ofra Golani and Suzana Horn and Mandel, \{Jacob J.\} and Noam Shental and Ayelet Shai and Shlomit Yust-Katz and Ravid Straussman",

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Nature America, Inc. 2025.",

year = "2025",

month = nov,

day = "14",

doi = "10.1038/s43018-025-01073-3",

language = "English",

volume = "6",

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journal = "Nature Cancer",

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Gigi, E, Gavert, N, Raijman-Nagar, L, Zwang, Y , Zemach, H , Livyatan, I, Levy-Barda, A, Laviv, Y, Kanner, AA, Amiel, A, Siegal, T, Leibovici, A, Selezen, I, Badran, O, Zohar, Y, Safadi, E, Prather, LL, Helfer, CR, Castro, P, Barshack, I, Dadosh, T , Levin-Zaidman, S , Goliand, I , Golani, O, Horn, S, Mandel, JJ, Shental, N, Shai, A, Yust-Katz, S & Straussman, R 2025, 'Characterization of the tumor microbiome of brain metastases and glioblastoma reveals tumor-type-specific and location-specific microbial signatures', Nature Cancer, vol. 6, no. 11, pp. 1761-1776. https://doi.org/10.1038/s43018-025-01073-3

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T1 - Characterization of the tumor microbiome of brain metastases and glioblastoma reveals tumor-type-specific and location-specific microbial signatures

AU - Gigi, Elinor

AU - Gavert, Nancy

AU - Raijman-Nagar, Lilach

AU - Zwang, Yaara

AU - Zemach, Hofit

AU - Livyatan, Ilana

AU - Levy-Barda, Adva

AU - Laviv, Yossi

AU - Kanner, Andrew A.

AU - Amiel, Alexandra

AU - Siegal, Tali

AU - Leibovici, Anca

AU - Selezen, Inna

AU - Badran, Omar

AU - Zohar, Yaniv

AU - Safadi, Esraa

AU - Prather, Lyndsey L.

AU - Helfer, Cassandra R.

AU - Castro, Patricia

AU - Barshack, Iris

AU - Dadosh, Tali

AU - Levin-Zaidman, Smadar

AU - Goliand, Inna

AU - Golani, Ofra

AU - Horn, Suzana

AU - Mandel, Jacob J.

AU - Shental, Noam

AU - Shai, Ayelet

AU - Yust-Katz, Shlomit

AU - Straussman, Ravid

PY - 2025/11/14

Y1 - 2025/11/14

N2 - Brain tumors, including glioblastoma multiforme (GBM) and brain metastases, present a notable clinical challenge. Recent research highlights the presence of intratumor bacteria across many tumor types, yet the microbiome of brain tumors remains largely underexplored. Here we show that the microbiome of 322 brain tumors differs markedly by tumor type and location. Using multiple approaches to visualize, culture and sequence bacterial communities, we found that brain metastases harbor higher bacterial richness and diversity than GBM, with distinct microbial compositions. Moreover, metastases in posterior brain regions exhibited greater diversity than those in anterior regions. Pathway analysis revealed enrichment of bacterial metabolic pathways associated with tumor spread and metastasis in brain metastases while GBM was enriched with pathways supporting alternative phosphorus use. These findings provide valuable insights into the microbial landscape of brain tumors, highlighting tumor-type-specific and location-specific variation and suggesting potential roles for bacteria in brain tumor biology.

AB - Brain tumors, including glioblastoma multiforme (GBM) and brain metastases, present a notable clinical challenge. Recent research highlights the presence of intratumor bacteria across many tumor types, yet the microbiome of brain tumors remains largely underexplored. Here we show that the microbiome of 322 brain tumors differs markedly by tumor type and location. Using multiple approaches to visualize, culture and sequence bacterial communities, we found that brain metastases harbor higher bacterial richness and diversity than GBM, with distinct microbial compositions. Moreover, metastases in posterior brain regions exhibited greater diversity than those in anterior regions. Pathway analysis revealed enrichment of bacterial metabolic pathways associated with tumor spread and metastasis in brain metastases while GBM was enriched with pathways supporting alternative phosphorus use. These findings provide valuable insights into the microbial landscape of brain tumors, highlighting tumor-type-specific and location-specific variation and suggesting potential roles for bacteria in brain tumor biology.

UR - https://www.scopus.com/pages/publications/105021808885

U2 - 10.1038/s43018-025-01073-3

DO - 10.1038/s43018-025-01073-3

M3 - Article

AN - SCOPUS:105021808885

SN - 1474-175X

VL - 6

SP - 1761

EP - 1776

JO - Nature Cancer

JF - Nature Cancer

IS - 11

ER -

Characterization of the tumor microbiome of brain metastases and glioblastoma reveals tumor-type-specific and location-specific microbial signatures

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