Antibiotic-induced disturbances of the gut microbiota result in accelerated breast tumor 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 ORCID: https://orcid.org/0000-0002-1379-2196, 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. ORCID: https://orcid.org/0000-0001-8938-5709 and Robinson, Stephen D. ORCID: https://orcid.org/0000-0002-6606-7588 (2021) Antibiotic-induced disturbances of the gut microbiota result in accelerated breast tumor 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 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.

Item Type: Article
Additional Information: Funding Information: This work was supported by funding from the UKRI Biotechnology and Biological Sciences Research Council (BBSRC) Norwich Research Park (NRP) Biosciences Doctoral Training Partnership (DTP) to S.D.R./B.M.K. (BB/J014524/1) and L.J.H./C.A.-G. (BB/M011216/1); the UKRI BBSRC NRP DTP as a National Productivity Investment Fund CASE Award in collaboration with BenevolentAI to M.M./T.K. (BB/S50743X/1); a Breast Cancer Now studentship to S.D.R./A.M.M. (2017NovPhD973); a BigC studentship to S.D.R./C.A.P. (18-15R); the Associazione Italiana per la Ricerca sul Cancro to E.T. (IG no 20264); a fellowship to TK in computational biology at the Earlham Institute (Norwich, UK) in partnership with the Quadram Institute Bioscience (Norwich, UK); strategic support from UKRI BBSRC to TK (BB/J004529/1, BB/P016774/1, and BB/CSP17270/1); a Wellcome Trust Investigator award to LJH (100974/C/13/Z); and strategic support from the UKRI BBSRC Institute Strategic Program Gut Microbes and Health BB/R012490/1 and its constituent projects BBS/E/F/000PR10353 and BBS/E/F/000PR10355 to G.L.G. T.K. L.J.H. and S.D.R. S.D.R. and W.J.F. were also supported by Cancer Research UK (grant number C18281/A29019). M.R.R. was supported by Susan G. Komen Career Catalyst award CCR17483602, IRG-17-097-31 (ACS), the University of Virginia Cancer Center, and support from NCI Cancer Center Support grant P30CA44570 as startup funds. T.Y.F. was supported by Farrow Fellowship and by the NCI Cancer Center Support Grant P30 CA44579. Additionally, we thank Norfolk Fundraisers, Mrs Margaret Doggett, and the Colin Wright Fund for their kind support and fundraising over the years.
Uncontrolled Keywords: cancer,microbiology,pathophysiology,general,sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/1000
Faculty \ School: Faculty of Science > School of Biological Sciences
Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 10 Aug 2021 01:28
Last Modified: 25 Sep 2022 02:21
URI: https://ueaeprints.uea.ac.uk/id/eprint/81026
DOI: 10.1016/j.isci.2021.103012

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