Clinical Study of Saliva Metabolomics and Microbiomics in Respiratory Diseases

Type

Student thesis: Master's ThesisMaster of Philosophy

Original languageEnglish
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Award date2018
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Abstract

Human saliva has received substantially less attention as a biofluid for the identification of novel biomarkers for diseases, albeit it reflects most of the compounds found in blood. Similarly, there are few studies on the lung microbiome or metabolome especially assessed through saliva as a biosample. In this clinical research study, it was established that certain metabolites and bacteria in saliva change in particular respiratory diseases, such as chronic
obstructive pulmonary disease (COPD) and lung cancer, allowing differentiation from healthy patients. The metabolomic fingerprints of saliva were derived from Flow Infusion Electrospray Mass Spectrometry. ANOVA of the derived data followed by Principal Component Analysis suggested that fingerprints could differentiate between several respiratory diseases (COPD, lung cancer, asthma, pneumonia, idiopathic pulmonary fibrosis, bronchiectasis, and sarcoidosis) and “healthy” controls. Some individual metabolites were tentatively identified
based on accurate mass predictions but more work is required to confirm these.
The microbiomes were assessed by 16S rRNA amplicon sequencing. Analysis at genus level identified 11 genera, which significantly differed between the experimental classes. Assessment of the core microbiome has shown that Streptococcus was prevalent in every saliva sample. The COPD Exacerbation class was associated with a loss in a range of bacterial genera as shown by estimates of a-diversity. However, these samples displayed an increase in Staphylococcus. Other genera were reduced in abundance and this was shown by saliva from
patients which were undergoing an exacerbation, had significantly lower bacterial loads when compared to the other categories. This in turn may offer insights with regards to the clinical features of respiratory diseases in relation to the levels of bacterial load during stable conditions or exacerbations.
The metabolomic and microbiomic approaches presented here, both show similar variations with respect to the classification of the pulmonary conditions and controls, which makes human saliva a reliable, cost-effective, non-invasive biofluid with prospective uses in novel methods of screening and diagnosing patients suffering of specific diseases, not only of the pulmonary nature

Keywords

  • human saliva, flow infusion electrospray mass spectrometry, amplicon sequencing, 16S bacterial gene, COPD, lung cancer, respiratory diseases