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Merck

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

iScience (2021-09-16)
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
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.

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Sigma-Aldrich
Terreno Eagle modificato di Dulbecco - alto glucosio, With 4500 mg/L glucose, L-glutamine, sodium pyruvate, and sodium bicarbonate, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Desossiribonucleasi I, Standardized vial containing 2,000 Kunitz units of DNase I (D4527), vial of ≥0.25 mg total protein
Sigma-Aldrich
Eosin Y Solution, Alcoholic
Sigma-Aldrich
Neomycin trisulfate salt hydrate, powder
Sigma-Aldrich
Hyaluronidase from sheep testes, Type V, lyophilized powder, ≥1,500 units/mg solid
Sigma-Aldrich
Amfotericina B, BioReagent, suitable for cell culture, ~80% (HPLC)
Sigma-Aldrich
Ampicillina
Sigma-Aldrich
Cromolyn sodium salt, ≥95%
Supelco
Metronidazole, analytical standard