Research Project Proposal (750-1000 words max.)

See Self-defined research project proposal (Summer 1) in the guidance for more information

Introduction

H. pylori is a gram negative bacterium that has infected approximately 50% of the world's population. This increases to 70% of the population of low and middle income countries (1). While most infected individuals do not experience symptoms when symptoms arise they include stomach pain, nausea and bloating. Additionally H. Pylori infection increases the risk of stomach ulcers, gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. If H. pylori is left untreated it will persist for life (2). Typically H. pylori is treated with 2 or 3 antibiotics and a proton pump inhibitor (3).  However, the high rates of infection combined with the rising levels of H. pylori antimicrobial resistance (4). means that many traditional methods of treating H. pylori infections are failing to cure patients. In fact the World Health Organisation has deemed clarithromycin resistant H. pylori as a high priority in  the area of antibiotic resistantance research and development (5).  As a result there has been a renewed interest in the development of novel therapeutics to treat H. pylori. In my project I am proposing an investigation into the use of chilli oil to target and treat H. pylori. This will be done by examining its effects against clinical isolates of H. pylori and by screening it with currently used antibiotics to see if it enhances their activity. Chilli oil has already been proven to have antimicrobial activity (6) and to have antiinflammatory properties (7). As chilli oil is inexpensive, easily accessible and already present in other conventional treatments it could potentially provide a very effective complementary therapy to traditional methods of treating H. pylori. This would be particularly important in developing countries where cost and access to antibiotics result in many cases of H. pylori going untreated. 

References: 

1. Bravo, D. et al. (2018) “helicobacter pylori in human health and disease: Mechanisms for local gastric and systemic effects,” World Journal of Gastroenterology, 24(28), pp. 3071–3089. Available at: https://doi.org/10.3748/wjg.v24.i28.3071. 
2. Smith, S.M., O’Morain, C. and McNamara, D. (2019) “Helicobacter pylori resistance to current therapies,” Current Opinion in Gastroenterology, 35(1), pp. 6–13. Available at: https://doi.org/10.1097/mog.0000000000000497. 
3. Helicobacter pylori (no date) HSE.ie. Available at: https://www.hse.ie/eng/services/list/2/gp/antibiotic-prescribing/conditions-and-treatments/gastro/helicobacter-pylori/helicobacter-pylori.html (Accessed: February 8, 2023). 
4. Wang, D. et al. (2019) “The antibiotic resistance of helicobacter pylori to five antibiotics and influencing factors in an area of China with a high risk of gastric cancer,” BMC Microbiology, 19(1). Available at: https://doi.org/10.1186/s12866-019-1517-4. 
5. Smith, S.M., O’Morain, C. and McNamara, D. (2019) “Helicobacter pylori resistance to current therapies,” Current Opinion in Gastroenterology, 35(1), pp. 6–13. Available at: https://doi.org/10.1097/mog.0000000000000497. 
6. A Omolo, M. (2014) “Antimicrobial properties of Chili Peppers,” Journal of Infectious Diseases and Therapy, 02(04). Available at: https://doi.org/10.4172/2332-0877.1000145. 
7. Lv, J. et al. (2015) “Consumption of spicy foods and total and cause specific mortality: Population based Cohort Study,” BMJ [Preprint]. Available at: https://doi.org/10.1136/bmj.h3942.

Project Methodology & Timeline

A broth microdilution assay will be used to test the antibacterial activity of different concentrations of chilli oil against H. pylori. By determining the minimum concentration of chilli oil needed to inhibit the growth of the H. pylori strains the antibacterial activity of chilli oil can be deduced.  The H. pylori strains will have been previously cultured from stomach tissues obtained during endoscopies.  This will be carried out using both antibiotic-susceptible and antibiotic resistant H. pylori strains. Growth inhibition will

be determined by measuring the absorbance of the broth cultures of H. pylori in the absence and presence of chilli oil using a spectrophotometer. A decrease in absorbance indicates growth inhibition. Chilli oil will also be tested in combination with antibiotics commonly used to treat H. pylori, such as clarithromycin, metronidazole and amoxicillin, in order to test whether the chilli oil enhances their activity. Taken together, these experiments will provide insight into the potential use of chilli oil for improving H. pylori eradication. Over the course of the 6 weeks I will attend  weekly meetings with a multidisciplinary team of scientists and clinicians to discuss the progress of my project and the data generated. 

Week 1: I will participate in my lab induction and get trained in the various lab methods and techniques I will be using throughout my project.  I will focus on reviewing the current literature. 

Week 2: I will determine whether or not chilli oil has an antimicrobial effect against H. pylori using broth microdilution assays.  This will allow me to determine the minimum inhibitory concentration of chilli oil against H. pylori. 

Week 3: I will repeat the experimental procedure from week 2 but this time using  various strains of antimicrobial resistant H. pylori. By the end of week 3 I will be able to compare my results and gather information about the antimicrobial effect of chilli oil on antimicrobial susceptible and antibiotic resistant H. pylori strains. 

Week 4: I will test my chilli oil dilutions in combination  with metronidazole and amoxicillin to see its impact on H. pylori strains. 

Week 5: This will be my last week of experimental work and here I will investigate how chilli oil in combination with clarithromycin inhibits the growth of H. pylori strains. 

Week 6: Once all of the data has been gathered I will analyse and discuss my results and use these to draw conclusions. I will develop my poster and look into any further applications of my research. I will have the opportunity to work and share my findings with the multidisciplinary team of doctors and scientists at the Trinity Academic Gastroenterology Group which will allow me to understand the clinical relevance of my findings in a number of different fields. 

Intended Outcomes

1. To gather data on the  antimicrobial activity of chilli oil  against H. pylori strains including antibiotic resistant strains of H. pylori. 
2. To gather data on chilli oils ability to enhance the antimicrobial effects of current antimicrobial therapies against H. pylori.
3. Taken together, the data generated from this project will provide evidence on whether further research into the use of chilli oil for H. pylori is warranted.

Planning for pre-approval requirements ( if relevant e.g. ethics approval, Garda vetting)

N/A

Planning for expected additional project costs (if relevant e.g. lab expenses, subscriptions, software, project-related travel)

I will be working in my supervisor's lab at the Trinity Academic Gastroenterology Group (TAGG) Research Centre at Tallaght University Hospital, which is affiliated with Trinity College Dublin.  TAGG is a multidisciplinary research centre of excellence with a multidisciplinary team comprising microbiologists, molecular biologists and clinicians to drive innovations in gastroenterology. All the necessary equipment required for this project  (including the antibiotic-susceptible and antibiotic resistant H. pylori strains) is available through the supervisors research facilities at the TAGG research centre. A sum of 800 euro is sought to contribute to the cost of laboratory reagents and other consumables required for the project e.g bacterial culture media, chilli oil, antibiotics and plastic ware. The lab expenses and the cost of living in Dublin for the duration of the project will be covered by the bursary from the Laidlaw project. 

Are there any other relevant details to your proposal e.g., interdisciplinary collaborations, potential for international travel, or links to existing projects or organisations?

For my project I will be working in  Trinity Academic Gastroenterology Group (TAGG) Research Centre at Tallaght University Hospital. This will allow me to work with a multidisciplinary team composed of scientists and doctors from a number of different backgrounds. By collaborating with researchers outside of my own field I will be able to learn new scientific techniques and I will be able to gain a number of different perspectives on potential applications. of my research.  I plan to do my Summer 2 LIA with ReAct. This is a global network that aims to develop and then advocate for innovative and holistic methods of treating antimicrobial resistance which links to the work I will be doing in Summer one. My project also links to the EU One Health Action Plan against Antimicrobial resistance  and the World Health Organisation Strategic Priorities on Antimicrobial Resistance as it is involved in the development of cost effective novel therapeutics for the treatment of bacteria. Finally, in 2024 I hope to apply to the Leiden International Biomedical Student Conference conference so that I can share my research with others and meet with the guest speakers and fellow students.