iScience (Sep 2021)
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
Affiliations
- Alastair M. McKee
- Gut Microbes and Health Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7AU, UK
- Benjamin M. Kirkup
- Gut Microbes and Health Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7AU, UK
- Matthew Madgwick
- Gut Microbes and Health Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7AU, UK; Earlham Institute, Norwich Research Park, Norwich, NR4 7UZ, UK
- Wesley J. Fowler
- Gut Microbes and Health Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7AU, UK
- Christopher A. Price
- Gut Microbes and Health Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7AU, UK
- Sally A. Dreger
- Gut Microbes and Health Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7AU, UK
- Rebecca Ansorge
- Gut Microbes and Health Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7AU, UK
- Kate A. Makin
- Faculty of Medicine and Health Sciences, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK
- Shabhonam Caim
- Gut Microbes and Health Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7AU, UK
- Gwenaelle Le Gall
- Faculty of Medicine and Health Sciences, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK
- Jack Paveley
- Gut Microbes and Health Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7AU, UK
- Charlotte Leclaire
- Gut Microbes and Health Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7AU, UK
- Matthew Dalby
- Gut Microbes and Health Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7AU, UK
- Cristina Alcon-Giner
- Gut Microbes and Health Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7AU, UK
- Anna Andrusaite
- Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary Medicine and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK
- Tzu-Yu Feng
- Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA 22908, USA
- Martina Di Modica
- Molecular Targeting Unit, Department of Research, Fondazione IRCCS Instituto Nazionale di Tumori, Milan, 20133, Italy
- Tiziana Triulzi
- Molecular Targeting Unit, Department of Research, Fondazione IRCCS Instituto Nazionale di Tumori, Milan, 20133, Italy
- Elda Tagliabue
- Molecular Targeting Unit, Department of Research, Fondazione IRCCS Instituto Nazionale di Tumori, Milan, 20133, Italy
- Simon W.F. Milling
- Centre for Immunobiology, Institute of Infection, Immunity and Inflammation, College of Medicine, Veterinary Medicine and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK
- Katherine N. Weilbaecher
- Department of Internal Medicine, Division of Molecular Oncology, Washington University in St Louis, St. Louis, MO, 63110, USA
- Melanie R. Rutkowski
- Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA 22908, USA
- Tamás Korcsmáros
- Gut Microbes and Health Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7AU, UK; Earlham Institute, Norwich Research Park, Norwich, NR4 7UZ, UK
- Lindsay J. Hall
- Gut Microbes and Health Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7AU, UK; Faculty of Medicine and Health Sciences, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK; Chair of Intestinal Microbiome, School of Life Sciences, ZIEL – Institute for Food & Health, Technical University of Munich, 85354 Freising, Germany; Corresponding author
- Stephen D. Robinson
- Gut Microbes and Health Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7AU, UK; School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, UK; Corresponding author
- Journal volume & issue
-
Vol. 24,
no. 9
p. 103012
Abstract
Summary: 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.