Volatile Organic Compound Profiling of Mouse Models of Intestinal Inflammation and Colon Carcinogenesis

Reade, SP
(2016) Volatile Organic Compound Profiling of Mouse Models of Intestinal Inflammation and Colon Carcinogenesis. PhD thesis, University of Liverpool.

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A non-invasive, inflammatory bowel disease (IBD)-specific biomarker would be clinically useful due to the often inaccurate and unpleasant current diagnostic methods. The duration and extent of IBD increases the risk for colorectal cancer (CRC) therefore non-invasive screening for CRC in patients with long-term IBD may lead to early detection of abnormal changes and improve the chance of survival. To date, human metabolomic studies have shown potential for the identification of a faecal marker of IBD, but are limited by variation from diet, environment and medication. The aim of this work was to report the first study using HS-SPME-GC- MS to detect the VOC faecal metabolome in commonly used mouse models of IBD and CRC. Using an optimized method, the identification of the healthy murine faecal VOC profile resulted in little variation between individual mice with a noted significant effect of gender and age. Comparison of healthy mouse to human found 39 and 62 VOCs respectively with 33% overlap between the two species, thereby demonstrating the more complex gut environment of humans. These studies led to the identification of a VOC profile, characterized by an increase in aldehydes and a decrease in alcohols, as a marker of acute diarrhoea, compared to a significantly different profile for chronic colitis, characterised by the presence of methyl ketones. In addition, VOC profiling is capable of detecting murine-specific metabolic signatures associated with premalignant lesions of the colon, providing rationale for the investigation of new non-invasive methods for early tumour detection. These results were supported by findings questioning the specificity of faecal calproctectin as a marker of IBD due to the increased levels of calprotectin found in both colitis and cancer groups, compared to healthy controls. In conclusion, we have provided evidence that the identification of disease-associated VOC concentration ranges combined with specific marker compounds would potentially increase the likelihood of finding an IBD-specific faecal VOC marker profile. This work has presented rationale for future studies to investigate further the true origin of these marker VOCs by performing both in vitro and further in vivo work. The investigation of the faecal metabolome of a number of different murine models in combination, rather than the use of a single mechanistic model may be provide a better reflection of human disease.

Item Type: Thesis (PhD)
Divisions: Faculty of Health and Life Sciences
Depositing User: Symplectic Admin
Date Deposited: 09 Aug 2016 10:39
Last Modified: 19 Jan 2023 07:35
DOI: 10.17638/03001721
  • Probert, CSJ
  • Pritchard, DM
URI: https://livrepository.liverpool.ac.uk/id/eprint/3001721