Our gastrointestinal tract faces the challenge of having to mount protective immune responses against invading pathogens while not activating these mechanisms against dietary antigens or normal enteric flora. Professor Fiona Powrie aims to characterize the cellular and molecular pathways that control intestinal homeostasis, and how these break down in inflammatory bowel disease and colon cancer.
This podcast presents the research done by Professor Powrie whilst working in the Nuffield Department of Medicine. Professor Powrie is now Head the Kennedy Institute of Rheumatology.
Our guts are home to trillions of intestinal bacteria and more immune cells than anywhere else in our bodies. Investigating the relationship between the two is vital as a breakdown can lead to diseases such as inflammatory bowel disease and bowel cancer, and is also linked to type 2 diabetes and obesity.
From Bench to Bedside
Ultimately, medical research must translate into improved treatments for patients. At the Nuffield Department of Medicine, our researchers collaborate to develop better health care, improved quality of life, and enhanced preventative measures for all patients. Our findings in the laboratory are translated into changes in clinical practice, from bench to bedside.
Q: What’s so special about our guts?
FP: Our guts are an inner-tube of life, you could consider, running from the mouth right through the body. They’re a major site through which pathogens can enter the body and cause disease. They’re also a major site – home – to a large number of intestinal bacteria that live there, literally trillions, and there are also more immune cells in the intestine than anywhere else in the body. It’s a really busy site and it’s absolutely crucial that the immune system there is able to distinguish the helpful bacteria from the harmful bacteria in order to maintain a balance for health.
Q: What happens when this relationship breaks down?
FP: It’s a long-standing relationship because humans have evolved with their intestinal bacteria over millennia and things usually work really well. But of course like in any relationship things can break down and when that’s the case the immune system will attack these beneficial bacteria the same way a dangerous disease inducing microbe would. And that can lead to a lot of inflammation and bowel diseases such as inflammatory bowel disease.
Q: Can your research help us treat inflammatory bowel disease and bowel cancer?
FP: We hope so. We certainly think that’s the case. We are trying to understand the relationship between our intestinal immune system, all the immune cells in the intestine, and these trillions of bacteria that live there. We’ve identified distinct populations of T cells called regulatory T cells that are able to control inflammatory responses, thus preventing these unwanted reactions to our helpful bacteria. In addition we’ve identified some of the pathways that promote inflammation when things do break down, so that we can design pharmaceutical interventions to be able to neutralise those. And some of those types of approaches are showing promise in the clinic.
Q: So why does your line of research matter, why should we put money into it?
FP: Inflammatory bowel disease is a very devastating disease. It affects young individuals with a very high degree of morbidity, compromising their lifestyles. But understanding the reaction between the intestinal immune system and the intestinal bacteria is relevant not only to local diseases in the gut, it really is an underpinning for health. Changes have now been linked to diseases as diverse as cancer, type 2 diabetes and obesity, and also influences whether we might respond to vaccinations. So it’s a very important fundamental aspect of human physiology.
Q: What are the most important lines of research that have developed over the past 5 or 10 years?
FP: I think it’s a very rapidly developing field and it’s extremely timely to be working in this area. One of the reasons is that genetic technologies have allowed us to characterise and describe these large numbers of bacterial communities that live in the gut. Previously we didn’t know much about them. Now we know there are hundreds of different species that are present in any one individual. We can start to see how these communities change in disease. But these of course are just correlative and the challenge now is to understand how bacterial products actually influence the immune system and how we can harness that to promote health.
Q: How does your research fit into translational medicine within the department?
FP: I think it’s very relevant because we are studying inflammatory bowel disease patients. We’re trying to understand which aspects of this dialogue between the immune system and intestinal bacteria breaks down, in which subsets of inflammatory bowel disease patients, so we might more specifically target things to what has actually gone wrong.