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

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 tum...

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Published in:iScience 2021-09, Vol.24 (9), p.103012-103012, Article 103012
Main Authors: 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, 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., Korcsmáros, Tamás, Hall, Lindsay J., Robinson, Stephen D.
Format: Article
Language:English
Subjects:
Cancer
Microbiology
Pathophysiology
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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. [Display omitted] •Microbiota disturbances promote tumor growth in several breast cancer models•Increased tumor volume positively correlates with stromal mast cell density•Supplementation with a commensal restores tumor growth to normal Pathophysiology; Microbiology; Cancer
ISSN:2589-0042
2589-0042
DOI:10.1016/j.isci.2021.103012