Charting human microbiome and metabolome changes in disease and stress

• Main Author: Cameron, Simon John
• Format: Dissertation
• Language: English
• Published: Aberystwyth University 2015

The role that the human microbiome and metabolome may play in health and disease is well established. To date however, research focus has centred on the human gut microbiome. The microbiome of the respiratory tract has received substantially less attention. Here, the respiratory microbiome of patients with lung cancer and chronic obstructive pulmonary disease, both diseases which have unmet clinical needs, was profiled. For lung cancer, several microbiome-derived biomarkers were detected that may allow, through a non-invasive sampling technique, for the diagnosis of disease status and stage. For chronic obstructive pulmonary disease (COPD), a number of functional differences in the lung microbiome of patients were identified, which may help to explain progression of the disease. Additionally, for lung cancer, metabolomic fingerprinting of sputum from patients revealed a number of metabolites with the ability to differentiate between negative and positive patients, but who presented with clinically-similar symptoms. Using the techniques developed in these clinically-focussed projects, studies of the human microbiome's temporal variability and its response to extreme physiological and environmental stress were completed. Longitudinal sampling of the saliva of healthy individuals over a one year period, showed that the salivary microbiome and metabolome is remarkably stable, but that there is some change in bacterial load. Human saliva is considered a valuable source of both microbiome and metabolome-derived biomarkers, and this work suggests that the comparison of samples collected at different time-points in the year is valid. By sampling members of the Trans-Antarctic Winter Traverse expedition, an analogy to how the human microbiome and metabolome may alter as a result of prolonged human space travel was possible. The salivary microbiome was shown to increase in bacterial load and diversity as a result of the environmental and physiological stresses of the expedition, whilst the stool microbiome was shown to maintain the individual differences evident before the start of the expedition. Additionally, the metabolome of stool, saliva, and blood plasma was shown to be stable throughout the expedition. This research project has shown that analysis of the human microbiome in areas not frequently studied by the field in general can provide novel insights into diseases with unmet clinical needs, and the role that both the microbiome and metabolome can have in the body's response to stress.