Antibiotic-induced disturbances of the gut microbiota result in accelerated breast tumor growth

Alastair M McKee; Benjamin M Kirkup; Matthew Madgwick; Wesley J Fowler; Christopher A Price; Sally A Dreger; Rebecca Ansorge; Kate A Makin; Shabhonam Caim; Gwenaelle Le Gall; Jack Paveley; Charlotte Leclaire; Matthew Dalby; Cristina Alcon-Giner; Anna Andrusaite; Tzu-Yu Feng; Martina Di Modica; Tiziana Triulzi; Elda Tagliabue; Simon W F Milling; Katherine N Weilbaecher; Melanie R Rutkowski; Tamás Korcsmáros; Lindsay J Hall; Stephen D Robinson

doi:10.1016/j.isci.2021.103012

Antibiotic-induced disturbances of the gut microbiota result in accelerated breast tumor growth

iScience. 2021 Aug 20;24(9):103012. doi: 10.1016/j.isci.2021.103012. eCollection 2021 Sep 24.

Authors

Alastair M McKee¹, Benjamin M Kirkup¹, Matthew Madgwick^{1

2}, Wesley J Fowler¹, Christopher A Price¹, Sally A Dreger¹, Rebecca Ansorge¹, Kate A Makin³, Shabhonam Caim¹, Gwenaelle Le Gall³, Jack Paveley¹, Charlotte Leclaire¹, Matthew Dalby¹, Cristina Alcon-Giner¹, Anna Andrusaite⁴, Tzu-Yu Feng⁵, Martina Di Modica⁶, Tiziana Triulzi⁶, Elda Tagliabue⁶, Simon W F Milling⁴, Katherine N Weilbaecher⁷, Melanie R Rutkowski⁵, Tamás Korcsmáros^{1

2}, Lindsay J Hall^{1

3

8}, Stephen D Robinson^{1

9}

Affiliations

¹ Gut Microbes and Health Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7AU, UK.
² Earlham Institute, Norwich Research Park, Norwich, NR4 7UZ, UK.
³ Faculty of Medicine and Health Sciences, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.
⁴ Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary Medicine and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK.
⁵ Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA 22908, USA.
⁶ Molecular Targeting Unit, Department of Research, Fondazione IRCCS Instituto Nazionale di Tumori, Milan, 20133, Italy.
⁷ Department of Internal Medicine, Division of Molecular Oncology, Washington University in St Louis, St. Louis, MO, 63110, USA.
⁸ Chair of Intestinal Microbiome, School of Life Sciences, ZIEL - Institute for Food & Health, Technical University of Munich, 85354 Freising, Germany.
⁹ School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK.

Abstract

The gut microbiota's function in regulating health has seen it linked to disease progression in several cancers. However, there is limited research detailing its influence in breast cancer (BrCa). This study found that antibiotic-induced perturbation of the gut microbiota significantly increases tumor progression in multiple BrCa mouse models. Metagenomics highlights the common loss of several bacterial species following antibiotic administration. One such bacteria, Faecalibaculum rodentium, rescued this increased tumor growth. Single-cell transcriptomics identified an increased number of cells with a stromal signature in tumors, and subsequent histology revealed an increased abundance of mast cells in the tumor stromal regions. We show that administration of a mast cell stabilizer, cromolyn, rescues increased tumor growth in antibiotic treated animals but has no influence on tumors from control cohorts. These findings highlight that BrCa-microbiota interactions are different from other cancers studied to date and suggest new research avenues for therapy development.

Keywords: Cancer; Microbiology; Pathophysiology.

Abstract

Grants and funding