Paediatric Respiratory Disease and the Microbiota: Noisy Signals and Opportunities for Intervention

Abstract

Respiratory illness is a global health challenge accounting for over 6 million premature deaths annually. Paediatric respiratory disease is particularly notable as both the largest cause of infant death as well as likely setting up conditions for adult disease development. Improving our understanding of paediatric respiratory diseases may therefore create better global respiratory health outcomes in both children and adults. The respiratory microbiota represents a relatively new tool to understand disease pathology, and potential therapeutic intervention points. This thesis aimed to both contextualise the microbiota of the respiratory tract across different diseases and to determine if current treatments for diseases particularly relevant to New Zealand altered the respiratory tract microbiota. A meta-analysis of 16S rRNA gene data spanning several diseases, research populations and anatomical sites, revealed evidence of both a common microbiota signature across all respiratory samples, and a more general disease-specific signature. This holds potential implications for future work in terms of identifying diagnostic biomarkers, and treatments which could commonly be applied across multiple diseases. Additionally, this vast collection of data shed light on the extent to which heterogeneity complicates inter-study comparisons. Differences in sample collection, laboratory and analytical techniques make distinguishing true biological differences from technical artefacts challenging. Statistical analysis of how much each factor influenced the microbiota demonstrated commonalities with previous investigations into the gastrointestinal microbiota with factors such as DNA extraction method explaining large amounts of underlying data variation. New Zealand has a higher than expected disease burden of several respiratory diseases including pneumonia and bronchiolitis - acute infections which place children at higher risk of later life disease - and bronchiectasis - a chronic disease potentially reversible only in children. Understanding the impact of current treatments on the microbiota could reveal new therapeutic windows. Here I present data indicating that the paediatric airway microbiota responded dynamically to treatments in a manner indicative of improved health status. This thesis adds to the growing body of literature covering the respiratory tract microbiota, both contextualizing previous information and providing new and important insights into the impacts of treatments on the microbiota.