Headspace Metabolomics for Non-invasive Biomarker Discovery

Recent developments in advanced mass spectrometry and data treatment tools have led to a boom in the efficient design of point-of-care testing (POCT). Approaches are based on novel disease biomarkers discovery with metabolomics studies and innovative sensor technologies. Breath analysis is an ideal candidate for POCT because of its non-intrusive nature; it is, however, much less developed than blood testing. Nevertheless, diseases as varied as lung and throat cancers, Parkinson's disease and pulmonary diseases have been shown to possess specific volatile biomarkers "fingerprint" which have been, to date, under-utilised. We propose therefore to move metabolomics to the headspace and study the volatilome of microbial communities to explore yet untapped opportunities for diagnostic and screening.
This project entails the development of a novel pipeline for biomarker discovery in the breath volatilome (volatile metabolites), in clinically-relevant scenarios. Focusing on the oral/gut microbiome (a complex community of bacteria living at the aerobic/anaerobic interface between mucosa and oral cavity), which influences oral health (cariogenesis, periodontitis, gingivitis) and systemic and cardio-metabolic health, we propose a unique transitional approach from bench to clinical practice.
During the project, analytical methods will be developed for non-targeted volatilomics using standard mixtures of representative volatile metabolites. This will include sampling, GC-MS analysis and data processing methods. Batch biofilm fermentation microcosms (in vitro) with then be ran with various treatments (such as carbon and nitrogen availability), making use of existing in vitro multi-species biofilm models established in Prof Gordon Ramage's lab. The statistical analysis tool of the pipeline will be adapted from existing tools in the Gauchotte-Lindsay group to the volatilome of these samples and biomarkers that correlate with the variations in treatment will be identified. Finally, volatilome characterisation will be carried out using the same analytical pipelines in groups of healthy human volunteers and volunteers with periodontitis and obesity-associated endotoxaemia before, during and after an intervention using dietary or pharmacological approaches to modulate the biofilm (in vivo). Here biomarkers that could eventually be employed in point-of-care sensors will be identified.



Aims and objectives:

This project will answer the question: Can we identify volatile biomarkers for oral health as a portal to systemic health using a novel metabolomics approach based on non-intrusive breath sampling?

The aim is to produce a shortlist of chemical compounds (optimal fingerprint) that could be employed in a low-cost point-of-care sensors or lab-on-a-chip.





Novelty of the research methodology:

Metabolomics studies have mostly been carried out in biological samples such as blood, urine or faeces. There is growing evidence that microbial activities regulate a broad range of functions in the human body and that patients with related illness(es) present different microbiome than healthy subjects. In turns, recent research also demonstrates that the chemical composition of the headspace above a microbial community is representative of the turned-on metabolic and catabolic pathways.

We propose therefore to move metabolomics to the headspace and study the volatilome of microbial communities to explore yet untapped opportunities for diagnostic and screening.