Assessing the microbiome mediated augmented volatile organic compounds response in oesophagogastric cancer
File(s)
Author(s)
Vadhwana, Bhamini
Type
Thesis
Abstract
Oesophagogastric cancer is the fifth most common cancer in England and Wales. Early non-specific symptoms are shared with benign disease presenting a diagnostic dilemma. There remains a clinical need to develop an acceptable, accurate and affordable method to identify high risk patients at an earlier stage.
The aim of this thesis is to investigate the role of augmenting target VOCs by exploiting the oral and tumour associated microbiome for accurate detection of early oesophagogastric cancer.
Microbial profiling with 16S rRNA gene sequencing (V3-V4) of oesophagogastric cancer tissue demonstrated Lactobacillus (p=0.04) and Pseudopropionibacterium (p=0.047) were significantly more abundant in gastric cancer.
Cultivated bacteria from matched tumour and saliva samples underwent Shotgun metagenomic analysis. Liquid cultures were established to monitor cell growth curves. Glucose, 0.1M concentration, was spiked into the culture and headspace VOCs extracted at the end log phase for two-dimensional gas-chromotography-mass spectrometry analysis. Medium chain fatty acids were increased following glucose introduction; (i) eicasonic acid 2.8-fold (ii) butanoic acid, 4-hydroxy 4.1-fold (iii) pentanoic acid, 3-methyl 10.7-fold. Predicted metabolic pathways demonstrated the potential role of multiple pathways in target end-metabolite production: succinate to propionate, pyruvate to acetate, glutamate to butyrate.
A clinical study was designed for patients to consume nutritional stimulant drinks and provide serial exhaled breath samples into the selected ion flow tube-mass spectrometer. Short chain fatty acids; butyric- and propanoic acids, were increased 10.5- and 4-fold respectively in gastric cancer. Butyric acid, propanoic acid and butanal were increased in both cancer types after glycerol consumption. A combination of amino acids demonstrated an increase in p-cresol.
This study supports the role of an augmented VOC breath test by exploiting the oral and tumour-associated microbiome. It offers a potentially novel non-invasive method to triage patients with non-specific upper gastrointestinal patients, facilitate earlier cancer detection and ultimately improve overall survival.
The aim of this thesis is to investigate the role of augmenting target VOCs by exploiting the oral and tumour associated microbiome for accurate detection of early oesophagogastric cancer.
Microbial profiling with 16S rRNA gene sequencing (V3-V4) of oesophagogastric cancer tissue demonstrated Lactobacillus (p=0.04) and Pseudopropionibacterium (p=0.047) were significantly more abundant in gastric cancer.
Cultivated bacteria from matched tumour and saliva samples underwent Shotgun metagenomic analysis. Liquid cultures were established to monitor cell growth curves. Glucose, 0.1M concentration, was spiked into the culture and headspace VOCs extracted at the end log phase for two-dimensional gas-chromotography-mass spectrometry analysis. Medium chain fatty acids were increased following glucose introduction; (i) eicasonic acid 2.8-fold (ii) butanoic acid, 4-hydroxy 4.1-fold (iii) pentanoic acid, 3-methyl 10.7-fold. Predicted metabolic pathways demonstrated the potential role of multiple pathways in target end-metabolite production: succinate to propionate, pyruvate to acetate, glutamate to butyrate.
A clinical study was designed for patients to consume nutritional stimulant drinks and provide serial exhaled breath samples into the selected ion flow tube-mass spectrometer. Short chain fatty acids; butyric- and propanoic acids, were increased 10.5- and 4-fold respectively in gastric cancer. Butyric acid, propanoic acid and butanal were increased in both cancer types after glycerol consumption. A combination of amino acids demonstrated an increase in p-cresol.
This study supports the role of an augmented VOC breath test by exploiting the oral and tumour-associated microbiome. It offers a potentially novel non-invasive method to triage patients with non-specific upper gastrointestinal patients, facilitate earlier cancer detection and ultimately improve overall survival.
Version
Open Access
Date Issued
2022-04-25
Date Awarded
12/01/2022
License URL
Advisor
Hanna, George
Boshier, Piers
Publisher Department
Department of Surgery & Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)