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 J. Dalby, Cristina Alcon-Giner, Anna Andrusaite, Tzu-Yu Feng, Martina Di Modica, Tiziana Triulzi, Elda Tagliabue, Simon W. F. MillingKatherine N. Weilbaecher, Melanie R. Rutkowski, Tamas Korcsmaros, Lindsay J. Hall, Stephen D. Robinson

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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.

Original languageEnglish
Article number103012
JournaliScience
Volume24
Issue number9
Early online date20 Aug 2021
DOIs
Publication statusPublished - 24 Sep 2021

Keywords

  • Cancer
  • Microbiology
  • Pathophysiology

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