Dr Tom Mules, a gastroenterologist at Hutt Hospital, has been recognised for his exceptional doctoral thesis on gut health. His research has earned him a place on The University of Otago's Division of Health Sciences list of exceptional doctoral theses.
Dr Stephen Inns, Primary Supervisor and Medical Lead for Research Capital, Coast and Hutt Valley, says Tom has been instrumental in enhancing gastroenterological research through his work at the Malaghan Institute of Medical Research and the completion of his PhD at the University of Otago. He noted that the prestigious Division of Health Sciences’ list “comprises only PhD candidates whose research is assessed as being of an exceptional quality, placing them in the top 10% of all theses examined”.
Tom shares insights into his PhD thesis (Helminths’ modulation of intestinal barrier function), his role as a clinical consultant at Health New Zealand | Te Whatu Ora and his research at the Malaghan Institute.
What is your PhD thesis about?
My thesis tackled the complex issue of why autoimmune and metabolic diseases are on the rise and how we might shift focus from treatment to prevention. I am interested in the ‘leaky’ gut theory, which proposes that the lining of our intestine is being compromised by an increase in exposure to harmful substances in our environment. This makes our gut more leaky, which can trigger inflammation and diseases in our intestine and other organs. To explore this theory and how we could strengthen a leaky gut to treat disease, I researched the effect of helminths, also called intestinal parasites, on the function of the intestinal barrier.
My findings showed that infection with certain helminths could reduce gut leakiness by reinforcing intestinal mucus, altering the gut environment (microbiome), and tightening the gaps between the cells which line the intestine. These findings suggest helminths could be used to treat autoimmune and inflammatory diseases caused by a leaky gut, such as Inflammatory Bowel Disease.
How exactly can helminths do this?
Helminths, particularly hookworm, have evolved to co-exist with humans over thousands of years. By altering our immune systems they can go undetected and continue to live in our bodies for many years. The changes they induce just happen to improve our intestinal barrier, thus making it less leaky. This means less bacteria and bacterial products can get through the intestinal layer, leading to a reduction in inflammation in our body.
Don’t all hookworms make you sick?
This can be the case in countries where helminths are endemic, where hookworm and other species of helminths are everywhere in the environment. In these countries, people become infected with large numbers of helminths and become sick. Hookworm requires tropical conditions to develop and infect others, so in Aotearoa and most urbanised countries we don’t have helminths. Our research suggests a controlled infection with a small number of hookworm is safe and could be beneficial in treating disease.
It’s worth explaining that there are many different species of hookworm. Human hookworm differ from hookworm carried by cats and dogs. Infection from those helminths will make you very sick.
Why helminths?
The hypothesis starts with epidemiology. People living in countries with lots of helminths have lower rates of these diseases. However, as these countries have become more sanitised and urbanised, helminth infections have decreased. Then, we found that infecting mice with helminths can protect them from lots of different diseases. This made us want to take this research one step further by trialing helminth therapy in patients.
What was the motivation behind your research?
We need to better understand the factors which are driving the dramatic increases in autoimmune, inflammatory, allergic and metabolic diseases. If we can address these factors, we could prevent these diseases from developing. The leaky gut theory is a plausible cause for these diseases becoming more common. With my research, I wanted to better understand the intestinal barrier and how we can make it less leaky.
What’s next with this research into gut health?
Gut health is so important and it’s great that people are taking greater interest in it and are starting to think more about the impact of dietary and lifestyle changes in disease prevention.
For hookworm therapy, we have learnt a lot but there is still a long way to go before it could be used in the clinic since there’s still many questions to investigate. For example:
• is the improvement in intestinal barrier function enough to treat a patient’s disease,
• do certain patients respond more favourably to hookworm therapy than others and how do we predict that response,
• what dose of hookworm should we use?
We are constantly coming up with new research questions which we need to explore.
How do you combine your clinical and research roles?
I currently work as a gastroenterologist three days a week at Hutt Hospital and as a researcher at the Malaghan Institute two days a week. The two roles are complementary. Having a foot in both camps means that I can be at the frontline, understanding the diseases affecting patients, and then try to address these issues through my research.
What would you say to someone who wanted to pursue some medical research?
I would highly encourage them to do so. Research is interesting and rewarding. It is a different pathway that medical practitioners can take and it can add huge value to our understanding of human disease. There isn’t enough emphasis on research in New Zealand.
As part of his PhD research, which was supported by the Health Research Council’s Clinical Research Training Fellowship, Dr Mules completed a pilot study using controlled helminth infections in a clinical trial setting. This study has laid the groundwork for larger trials and could offer a new avenue for patient treatment. At the start of the study, he was interviewed by RNZ. You can listen to the interview here.
