The bacterial microbiome modulates the initiation of brain metastasis by impacting the gut-to-brain axis
Summary: Brain metastases (BrMs) are the most common brain tumors in patients and are associated with poor prognosis. Investigating the systemic and environmental factors regulating BrM biology represents an important strategy to develop effective treatments. Toward this goal, we explored the contri...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004225001348 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1825206850380890112 |
|---|---|
| author | Matteo Massara Michelle Ballabio Bastien Dolfi Golnaz Morad Vladimir Wischnewski Eleni Lamprou Joao Lourenco Stéphanie Claudinot Hector Gallart-Ayala Rui Santalla Méndez Annamaria Kauzlaric Nadine Fournier Ashish V. Damania Matthew C. Wong Julijana Ivanisevic Nadim J. Ajami Jennifer A. Wargo Johanna A. Joyce |
| author_facet | Matteo Massara Michelle Ballabio Bastien Dolfi Golnaz Morad Vladimir Wischnewski Eleni Lamprou Joao Lourenco Stéphanie Claudinot Hector Gallart-Ayala Rui Santalla Méndez Annamaria Kauzlaric Nadine Fournier Ashish V. Damania Matthew C. Wong Julijana Ivanisevic Nadim J. Ajami Jennifer A. Wargo Johanna A. Joyce |
| author_sort | Matteo Massara |
| collection | DOAJ |
| description | Summary: Brain metastases (BrMs) are the most common brain tumors in patients and are associated with poor prognosis. Investigating the systemic and environmental factors regulating BrM biology represents an important strategy to develop effective treatments. Toward this goal, we explored the contribution of the gut microbiome to BrM development by using in vivo breast-BrM models under germ-free conditions or antibiotic treatment. This revealed a detrimental role of gut microbiota in fostering BrM initiation. We thus evaluated the impact of antibiotics and BrM outgrowth on the gut-brain axis. We found the bacterial genus Alistipes was differentially present under antibiotic treatment and BrM progression. In parallel, we quantified circulating metabolites, revealing kynurenic acid as a differentially abundant molecule that impaired the interaction between cancer cells and the brain vasculature in ex vivo functional assays. Together, these results illuminate the potential role of gut microbiota in modulating breast-BrM via the gut-to-brain axis. |
| format | Article |
| id | doaj-art-1ffa06371640427e852e4d3e45a814b8 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-1ffa06371640427e852e4d3e45a814b82025-02-07T04:48:04ZengElsevieriScience2589-00422025-02-01282111874The bacterial microbiome modulates the initiation of brain metastasis by impacting the gut-to-brain axisMatteo Massara0Michelle Ballabio1Bastien Dolfi2Golnaz Morad3Vladimir Wischnewski4Eleni Lamprou5Joao Lourenco6Stéphanie Claudinot7Hector Gallart-Ayala8Rui Santalla Méndez9Annamaria Kauzlaric10Nadine Fournier11Ashish V. Damania12Matthew C. Wong13Julijana Ivanisevic14Nadim J. Ajami15Jennifer A. Wargo16Johanna A. Joyce17Department of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Centre Lausanne, 1011 Lausanne, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, SwitzerlandDepartment of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Centre Lausanne, 1011 Lausanne, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, SwitzerlandDepartment of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Centre Lausanne, 1011 Lausanne, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, SwitzerlandDepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USADepartment of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Centre Lausanne, 1011 Lausanne, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, SwitzerlandDepartment of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Centre Lausanne, 1011 Lausanne, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, SwitzerlandAgora Cancer Research Centre Lausanne, 1011 Lausanne, Switzerland; Translational Data Science Facility, Swiss Institute of Bioinformatics, AGORA Cancer Research Centre, 1011 Lausanne, SwitzerlandGerm-free facility, Centre Hospitalier Universitaire Vaudois and University of Lausanne, 1066 Epalinges, SwitzerlandMetabolomics Unit, Faculty of Biology and Medicine, University of Lausanne, Lausanne, SwitzerlandDepartment of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Centre Lausanne, 1011 Lausanne, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, SwitzerlandAgora Cancer Research Centre Lausanne, 1011 Lausanne, Switzerland; Translational Data Science Facility, Swiss Institute of Bioinformatics, AGORA Cancer Research Centre, 1011 Lausanne, SwitzerlandAgora Cancer Research Centre Lausanne, 1011 Lausanne, Switzerland; Translational Data Science Facility, Swiss Institute of Bioinformatics, AGORA Cancer Research Centre, 1011 Lausanne, SwitzerlandPlatform for Innovative Microbiome & Translational Research (PRIME-TR), Moon Shots™, Houston, TX 77054, USAPlatform for Innovative Microbiome & Translational Research (PRIME-TR), Moon Shots™, Houston, TX 77054, USAMetabolomics Unit, Faculty of Biology and Medicine, University of Lausanne, Lausanne, SwitzerlandPlatform for Innovative Microbiome & Translational Research (PRIME-TR), Moon Shots™, Houston, TX 77054, USADepartment of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USA; Platform for Innovative Microbiome & Translational Research (PRIME-TR), Moon Shots™, Houston, TX 77054, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77054, USADepartment of Oncology, University of Lausanne, 1011 Lausanne, Switzerland; Ludwig Institute for Cancer Research, University of Lausanne, 1011 Lausanne, Switzerland; Agora Cancer Research Centre Lausanne, 1011 Lausanne, Switzerland; L. Lundin and Family Brain Tumor Research Center, Departments of Oncology and Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland; Corresponding authorSummary: Brain metastases (BrMs) are the most common brain tumors in patients and are associated with poor prognosis. Investigating the systemic and environmental factors regulating BrM biology represents an important strategy to develop effective treatments. Toward this goal, we explored the contribution of the gut microbiome to BrM development by using in vivo breast-BrM models under germ-free conditions or antibiotic treatment. This revealed a detrimental role of gut microbiota in fostering BrM initiation. We thus evaluated the impact of antibiotics and BrM outgrowth on the gut-brain axis. We found the bacterial genus Alistipes was differentially present under antibiotic treatment and BrM progression. In parallel, we quantified circulating metabolites, revealing kynurenic acid as a differentially abundant molecule that impaired the interaction between cancer cells and the brain vasculature in ex vivo functional assays. Together, these results illuminate the potential role of gut microbiota in modulating breast-BrM via the gut-to-brain axis.http://www.sciencedirect.com/science/article/pii/S2589004225001348MicroenvironmentMicrobiomeCancer |
| spellingShingle | Matteo Massara Michelle Ballabio Bastien Dolfi Golnaz Morad Vladimir Wischnewski Eleni Lamprou Joao Lourenco Stéphanie Claudinot Hector Gallart-Ayala Rui Santalla Méndez Annamaria Kauzlaric Nadine Fournier Ashish V. Damania Matthew C. Wong Julijana Ivanisevic Nadim J. Ajami Jennifer A. Wargo Johanna A. Joyce The bacterial microbiome modulates the initiation of brain metastasis by impacting the gut-to-brain axis iScience Microenvironment Microbiome Cancer |
| title | The bacterial microbiome modulates the initiation of brain metastasis by impacting the gut-to-brain axis |
| title_full | The bacterial microbiome modulates the initiation of brain metastasis by impacting the gut-to-brain axis |
| title_fullStr | The bacterial microbiome modulates the initiation of brain metastasis by impacting the gut-to-brain axis |
| title_full_unstemmed | The bacterial microbiome modulates the initiation of brain metastasis by impacting the gut-to-brain axis |
| title_short | The bacterial microbiome modulates the initiation of brain metastasis by impacting the gut-to-brain axis |
| title_sort | bacterial microbiome modulates the initiation of brain metastasis by impacting the gut to brain axis |
| topic | Microenvironment Microbiome Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2589004225001348 |
| work_keys_str_mv | AT matteomassara thebacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT michelleballabio thebacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT bastiendolfi thebacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT golnazmorad thebacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT vladimirwischnewski thebacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT elenilamprou thebacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT joaolourenco thebacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT stephanieclaudinot thebacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT hectorgallartayala thebacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT ruisantallamendez thebacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT annamariakauzlaric thebacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT nadinefournier thebacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT ashishvdamania thebacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT matthewcwong thebacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT julijanaivanisevic thebacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT nadimjajami thebacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT jenniferawargo thebacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT johannaajoyce thebacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT matteomassara bacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT michelleballabio bacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT bastiendolfi bacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT golnazmorad bacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT vladimirwischnewski bacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT elenilamprou bacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT joaolourenco bacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT stephanieclaudinot bacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT hectorgallartayala bacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT ruisantallamendez bacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT annamariakauzlaric bacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT nadinefournier bacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT ashishvdamania bacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT matthewcwong bacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT julijanaivanisevic bacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT nadimjajami bacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT jenniferawargo bacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis AT johannaajoyce bacterialmicrobiomemodulatestheinitiationofbrainmetastasisbyimpactingtheguttobrainaxis |