Low-biomass human microbiomes: another piece to the puzzle for non-communicable diseases

Abstract

The prevalence of non-communicable diseases (NCDs), such as cancers, cardiovascular, respiratory, and autoimmune diseases, has been increasing since the 1950s. Genetic, environmental and lifestyle factors, including diet, smoking status, and urbanisation, have all been identified as significant contributors to NCDs. More recently, the microbial communities of the human body (microbiota) have also been linked to NCDs. These communities typically exist in a mutually beneficial relationship with their human host, performing critical functions that the human body cannot perform itself. However, an imbalance to these communities may be a causal or perpetuating factor in diseases. While new research has started to unravel the interactions and effects that microbiota have on the human host, the majority of these studies have been focused primarily on the gut, with other body sites remaining neglected. Understanding microbiota of body sites other than the gut may provide further insight into the cause and effect of NCDs. These ‘non-gut’ microbiota still play vital roles for the human host, such as defence against pathogens on the skin, or homeostasis of the mouth to prevent or reduce caries and periodontal diseases. However, most microbiota technologies were developed to study the gut, a body site rich in microbial biomass. Hence, application of these technologies to samples from low biomass body sites is difficult due to overwhelming background levels of DNA and contamination. Nevertheless, sufficient information can be obtained from low microbial biomass samples when treated appropriately, and they provide another layer to unravelling the causes of NCDs. This thesis provides new perspectives on NCDs through the investigation of low microbial biomass body sites. I advocate for the human microbiome (microbiota, their genetic material and surrounding micro-environment) to be used as a new tool in pathology to understand both communicable and NCDs, while also highlighting techniques that can be used to mitigate contamination of low microbial biomass samples. Using a systems biology approach in combination with the microbiome provides a holistic approach to understanding NCDs, which I further explore through a perspectives piece. I then consider NCDs from a ‘non-gut’ microbiota perspective across three different studies: I track changes to skin and nasal microbiota after exposure to urban green spaces to improve the understanding of human-environmental interactions and the importance this has for immune-mediated diseases; I investigate the development of oral and lung microbiota in preterm infants and provide insights of a disruption to oral microbiota development in these infants, which can have long-lasting impacts on the immune system; and finally, I trace changes in oral microbiota of children with type 1 diabetes and hyperlipidaemic parents, which shows that changes to fat metabolism in the gut may have repercussions on oral microbiota. Through these three case studies, I provide a deeper understanding on how ‘non-gut’ microbiota change in response to the environment, which is especially critical in the microbiome development throughout immune training and the prevention of NCDs. Overall, this thesis provides the groundwork for a holistic approach to understand NCDs. Moving forward, considering the relationships between host genetics, the environment, and microbiota of all body sites will be vital for the treatment, cure, and prevention of NCDs.