The bacterial microbiome modulates the initiation of brain metastasis by impacting the gut-to-brain axis
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 <i>in vivo</i> 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 <i>Alistipes</i> 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 <i>ex vivo</i> functional assays. Together, these results illuminate the potential role of gut microbiota in modulating breast-BrM via the gut-to-brain axis.
Authors
- Annamaria Kauzlaric
- Johanna A. Joyce (ORCID: https://orcid.org/0000-0002-6332-2598)
- Bastien Dolfi (ORCID: https://orcid.org/0009-0005-3816-3379)
- Nadim J. Ajami (ORCID: https://orcid.org/0000-0002-3808-8576)
- Matthew C. Wong (ORCID: https://orcid.org/0000-0002-6317-2526)
- Jennifer Ann Wargo (ORCID: https://orcid.org/0000-0003-3438-7576)
- João Lourenço (ORCID: https://orcid.org/0000-0001-6549-5209)
- Nadine Fournier (ORCID: https://orcid.org/0000-0002-9347-7929)
- Golnaz Morad (ORCID: https://orcid.org/0000-0002-9460-618X)
- Eleni Lamprou (ORCID: https://orcid.org/0000-0002-5179-3018)
- Rui Santalla Méndez (ORCID: https://orcid.org/0000-0001-6851-9624)
- Ashish Damania (ORCID: https://orcid.org/0009-0001-3158-2846)
- Stéphanie Claudinot (ORCID: https://orcid.org/0000-0002-0190-1586)
- Vladimir Wischnewski (ORCID: https://orcid.org/0000-0002-9059-1304)
- Julijana Ivanišević (ORCID: https://orcid.org/0000-0001-8267-2705)
- Matteo Massara (ORCID: https://orcid.org/0000-0001-6724-5633)
- Héctor Gallart‐Ayala (ORCID: https://orcid.org/0000-0003-2333-0646)
- Michelle Ballabio
Institutions
- SIB Swiss Institute of Bioinformatics (CH)
- The University of Texas MD Anderson Cancer Center (US)
- Centre Hospitalier Universitaire Vaudois (CH)
- Ludwig Cancer Research (CH)
- Translational Research Platform for Veterinary Biologicals (India) (IN)
- University of Lausanne (CH)
Publication Details
- Journal
- iScience
- Published
- 2025-01-22
- DOI
- https://doi.org/10.1016/j.isci.2025.111874
- Citations
- 6
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 4.84
Funders
- Breast Cancer Research Foundation
- Ludwig Institute for Cancer Research
- Mark Foundation For Cancer Research
- European Commission
- Associazione Italiana per la Ricerca sul Cancro
- Université de Lausanne
- Centre Hospitalier Universitaire Vaudois
- National Institutes of Health
- Stand Up To Cancer
- Horizon 2020 Framework Programme
- National Cancer Institute