The Complexities of Long Distance: a relationship between the gut microbiota and breast cancer

Mckee, Alastair (2023) The Complexities of Long Distance: a relationship between the gut microbiota and breast cancer. Doctoral thesis, University of East Anglia.

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Abstract

Antibiotic induced perturbations of the gut microbiota are increasingly associated with the progression of several cancers. In contrast, the promotion of a healthy microbiota, often through probiotic supplementation, can improve treatment outcomes and bolster anti-cancer immune responses in tumours. However, studies involving breast cancer specifically are relatively limited. In 2020, breast cancer was the most frequently diagnosed cancer globally and carried one of the highest mortality rates among all cancer types. Additionally, the use of antibiotics in breast cancer treatment pathways is common. Thus, the research presented in this thesis aims to expand the current understanding of the influences the microbiota has on breast cancer, particularly regarding the downstream effects of antibiotic administration. The results demonstrate that antibiotic-induced perturbations of the microbiota promote primary breast cancer tumour progression in at least two different orthotopic models of the disease. Antibiotics did not influence tumour progression in germ-free animals, confirming that this progression was microbiota dependent. Single cell transcriptomics and histological analysis identified mast cells as being increased in tumours from antibiotic treated animals and, subsequently, inhibiting mast cell function rescued tumour growth in antibiotic treated animals to sizes similar to those observed in a control group at the same timepoint. Shotgun metagenomic sequencing of caecal samples identified reductions in several bacterial species in antibiotic treated animals. One such species, Faecalibaculum rodentium, has known anti-tumourigenic influence in colorectal cancer models and, when supplemented to antibiotic treated animals, rescued tumour growth. Efforts were made to investigate how perturbation of the microbiota influenced breast cancer metastasis, but the results obtained suggest further research is required to fully understand such influences. The implications of this research suggest that the use of antibiotics in breast cancer treatment pathways should be cautious and clinical guidance regarding their administration may need to be revised.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Chris White
Date Deposited:	16 Feb 2023 15:31
Last Modified:	16 Feb 2023 15:31
URI:	https://ueaeprints.uea.ac.uk/id/eprint/91158
DOI:

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