Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Microbiology and Immunology

Supervisor

Dr. Gregor Reid

Abstract

The collective microbes and their genomic activity within us, referred to as the human microbiome, is crucial in maintaining health, and disruptions in composition and activity have been associated with various diseases. Considering the importance of breast milk in neonatal development and the high rate of breast cancer in women, the objective of my thesis was to obtain a comprehensive analysis of the microbiota of the mammary glands and to examine the influence of these organisms on health and disease.

Human milk is an important source of bacteria for the developing infant. While a variety of studies over the last 20 years have provided a greater appreciation for how diverse and variable the milk microbiota is, little is known about these bacterial communities. Many studies have emphasized the adverse effects of antibiotics on the infant microbiota, however the impact of drugs on the lactating mother has not been studied. In Chapter 2 we report the changes caused by chemotherapy (over a 4 month period) on the milk microbiota and metabolome of a woman undergoing treatment for Hodgkin’s lymphoma. In Chapter 3, we show from a study of 39 Canadian women that neither gestation, mode of delivery nor gender of the child explains the diversity of the milk microbiota.

As milk is not sterile and given the nutrient-rich fatty composition of the breast and its exposure to the external environment via the nipple, we hypothesized that breast tissue has its own indigenous microbiota. In Chapter 4, we confirmed this in a study of breast tissue from 81 Canadian and Irish women, with the discovery of diverse bacterial communities dominated by the phylum Proteobacteria. To determine whether this tissue microbiota could play a role in breast cancer development, we compared, in Chapter 5, bacterial profiles in tissue between women with breast cancer and those who were disease free. We show that differences do exist and that women with cancer have higher numbers of bacteria with the ability to induce host DNA damage.

This work forms the platform for further studies that examine how breast milk and tissue are first colonized and how these microbiotas can be manipulated to promote optimal maternal and infant health.

Chapter2_Dataset_2-1.xlsx (9 kB)
metadata

Chapter2_Dataset_2-2.xlsx (38 kB)
metabolite raw data

Chapter3_Dataset_3-1.xlsx (41 kB)
metadata

Chapter3_Dataset_3-2.xlsx (35 kB)
OTU annotations

Chapter3_Dataset_3-3.xlsx (138 kB)
Aldex2 raw data

Chapter4_Dataset_4-1.xlsx (17 kB)
metadata

Chapter4_Dataset_4-2.xlsx (32 kB)
OTU annotations

Chapter5_Dataset_5-1.xlsx (17 kB)
metadata

Chapter5_Dataset_5-2.xlsx (23 kB)
aldex2 raw data

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