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

Mckee A, Kirkup B, Madgwick M, Fowler W, Price C, Dreger S, Ansorge R, Makin K, Caim S, Le Gall G, Pavely J, Leclaire C, Dalby M, Alcon-Giner C, Andrusaite A, Feng TY, Di Modica M, Triulzi T, Tagliabue E, Milling S, Weilbaecher K, Rutkowski M, Korcsmaros T, Hall L, Robinson S. (2021)

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The gut microbiotas function in regulating host immune and metabolic pathways has seen it linked to disease occurrence and progression in several cancers, namely melanoma, colon and liver cancer. However, there is limited research detailing its influence in breast cancer (BrCa), the cancer with the highest global occurrence and second highest mortality rate. 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 tumour growth when supplemented to tumour bearing animals following a course of antibiotics. Single cell transcriptomics of tumours from antibiotic treated mice identified an increased number of cells with a stromal signature and histology revealed an increased abundance of mast cells in the stromal regions of these tumours. We show that administration of a mast cell stabiliser, cromolyn, rescues increased tumour growth in animals treated with antibiotics but has no influence on tumours from vehicle treated 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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