E-Thesis 133 views
Investigating the potential for probiotic bacteria to be used as biotherapeutic interventions for colorectal cancer / CAITLIN MAGGS
Swansea University Author: CAITLIN MAGGS
Abstract
Colorectal cancer (CRC) is the second highest cause of cancer-related deaths globally. First-line treatments include surgical resection, immunotherapy and chemotherapy - whereby 5-fluorouracil (5FU) is a well-established chemotherapeutic agent. Recent studies have implicated specific bacterial speci...
| Published: |
Swansea, Wales, UK
2023
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| Institution: | Swansea University |
| Degree level: | Master of Research |
| Degree name: | MRes |
| Supervisor: | Facey, Paul. |
| URI: | https://cronfa.swan.ac.uk/Record/cronfa65062 |
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| Abstract: |
Colorectal cancer (CRC) is the second highest cause of cancer-related deaths globally. First-line treatments include surgical resection, immunotherapy and chemotherapy - whereby 5-fluorouracil (5FU) is a well-established chemotherapeutic agent. Recent studies have implicated specific bacterial species within the gastrointestinal tract (GIT) microbiome as drivers of tumorigenesis – with these species more-or-less omnipresent in colorectal tumours. Indeed, a higher abundance of pathogenic bacteria, such as Fusobacterium nucleatum, Bacteroides fragilis, Escherichia coli, Klebsiella pneumoniae, Salmonella typhimurium and Enterococcus faecalis have been observed in the microbiome of CRC patients. Indeed, these species, which are normally present at low titre in the gut, appear to be significantly overrepresented in CRC patients. Moreover, and perhaps more insidiously, these species have been shown to significantly drive carcinogenesis. Of further interest is the fact that 5FU, the main chemotherapeutic agent used to treat colorectal tumours, also appears to enrich the gut microbiome for these species. Thus, there is a demand for the development of biotherapeutic interventions that are resistant to 5FU and can also ameliorate this dysbiosis. One way that has been suggested is through the use of probiotic supplements. Probiotics are comprised of putative health-promoting bacteria and their ingestion may have the ability to balance the gut microbiome with more ‘healthy’ bacteria. This project will 1. Screen a panel of probiotics to identify strains that are resistant to 5FU, 2. Screen a panel of probiotics to ascertain whether they inhibit CRC-pathogenic bacterial species, 3. Investigate the metabolism preventing the toxic effects and reduced efficacy seen when 5FU is metabolised by certain microbiota members. This will provide insight into whether the probiotic strains have the potential to prevent the occurrence and/or recurrence of CRC via modulation of the CRC gut microbiota. |
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| Keywords: |
Probiotics, gut microbiota, microbiology, colorectal cancer |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
KESS2 and Cultech Ltd. |