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

McKee, Alastair M., Kirkup, Benjamin M., Madgwick, Matthew, Fowler, Wesley J., Price, Christopher A., Dreger, Sally A., Ansorge, Rebecca, Makin, Kate A., Caim, Shabhonam, Le Gall, Gwenaelle, Paveley, Jack, Leclaire, Charlotte, Dalby, Matthew J., Alcon-Giner, Cristina, Andrusaite, Anna, Feng, Tzu-Yu, Di Modica, Martina, Triulzi, Tiziana, Tagliabue, Elda, Milling, Simon W. F., Weilbaecher, Katherine N., Rutkowski, Melanie R., Korcsmaros, Tamas, Hall, Lindsay J. and Robinson, Stephen D. (2021) Antibiotic-induced disturbances of the gut microbiota result in accelerated breast tumour growth. iScience, 24 (9). ISSN 2589-0042

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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 tumour progression in multiple BrCa mouse models. Metagenomics highlight the common loss of several bacterial species following antibiotic administration. One such bacteria, Faecalibaculum rodentium, rescued this increased tumour growth. Single cell transcriptomics identified an increased number of cells with a stromal signature in tumours and subsequent histology revealed an increased abundance of mast cells in the tumour stromal regions. We show that administration of a mast cell stabiliser, cromolyn, rescues increased tumour growth in antibiotic treated animals but has no influence on tumours 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.

Item Type: Article
Faculty \ School: Faculty of Science > School of Biological Sciences
Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: LivePure Connector
Date Deposited: 10 Aug 2021 01:28
Last Modified: 19 Sep 2021 01:09
URI: https://ueaeprints.uea.ac.uk/id/eprint/81026
DOI: 10.1016/j.isci.2021.103012

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