PT  - JOURNAL ARTICLE
AU  - Benjamin M. Kirkup
AU  - Alastair M. McKee
AU  - Matthew Madgwick
AU  - Christopher A Price
AU  - Sally A Dreger
AU  - Kate A Makin
AU  - Shabhonam Caim
AU  - Gwenaelle Le Gall
AU  - Jack Paveley
AU  - Charlotte Leclaire
AU  - Matthew Dalby
AU  - Cristina Alcon-Giner
AU  - Anna Andrusaite
AU  - Martina Di Modica
AU  - Tiziana Triulzi
AU  - Elda Tagliabue
AU  - Simon WF Milling
AU  - Katherine N Weilbaecher
AU  - Tamas Korcsmáros
AU  - Lindsay J Hall
AU  - Stephen D Robinson
TI  - Antibiotic-induced disturbances of the gut microbiota result in accelerated breast tumour growth via a mast cell-dependent pathway
AID  - 10.1101/2020.03.07.982108
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.03.07.982108
4099  - http://biorxiv.org/content/early/2020/03/08/2020.03.07.982108.short
4100  - http://biorxiv.org/content/early/2020/03/08/2020.03.07.982108.full
AB  - The diverse community of commensal microbes that comprise the gut microbiota is known to play an integral role in human health, not least through its ability to regulate host immune responses and metabolic pathways. Alterations to the homeostasis of this community, including through the use of broad-spectrum antibiotics, have already been associated with the progression of several cancers, namely melanoma and liver. The aggressive nature of breast cancer (BrCa), largely due to its ability to metastasize early, has ranked the disease with the second highest mortality rate of all cancers globally. Yet the body of research into the complex relationship between the microbiota and BrCa is still limited. This study found that a depletion of the microbiota, through the administration of antibiotics, significantly increased the rate of primary tumour progression in mouse BrCa models. We show that antibiotic-induced microbiota disturbances lead to changes in behaviour of a relatively obscure tumour-immune cell population: mast cells. We observed increases in tumour stroma-associated mast cells in antibiotic treated animals. Moreover, inhibition of mast cell degranulation, via cromolyn, slowed tumour progression in antibiotic treated animals but not in control animals. Thus, it appears that a perturbed microbiota drives stroma-associated mast cell recruitment and activation, which in turn promotes primary tumour growth through an as yet unknown mechanism.One Sentence Summary: We show that breast cancer progression is accelerated through a unique/novel immune response involving mast cells as a result of an antibiotic induced perturbation of the gut microbiota in a mouse model.