Gut bacteria clinical study could help reduce radiotherapy side-effects

Date:
24 March 2014

Researchers will examine the role of gut bacteria in influencing the side-effects patients experience after radiotherapy, in the first clinical study of its type.

The study will be carried out by researchers at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust alongside colleagues from Imperial College London.

One important side-effect of radiotherapy to the abdomen is gut problems, which are thought to be partly caused by the effect of radiation on gut bacteria. These bacteria – as explained in a recent post on The Institute of Cancer Research’s (ICR) Science Talk blog – are crucial in maintaining a healthy gut.

The study will examine how gut bacteria affect treatment response in 330 patients with prostate cancer who have had or are due to undergo radiotherapy, and is funded by the NIHR Biomedical Research Centre (BRC) at The Royal Marsden and ICR, and the BRC at Imperial College. The study is a collaboration between the ICR and Imperial College London under their new joint Centre for Systems Oncology and Cancer Innovation.

The study also relies on the expertise of clinicians from The Royal Marsden’s Gastrointestinal Unit – a unique treatment and research unit with world-leading expertise in the effects of radiation on bowel function – and support from the Portugal-based Gulbenkian Foundation.

Study leader Professor David Dearnaley, Professor of Uro-Oncology at the ICR and Honorary Consultant at The Royal Marsden, said:

“Our study is the first to look scientifically at the influence of gut bacteria on how people with cancer respond to radiation treatment.  The ultimate aims of our work in this area are to reduce the severity of bowel problems after pelvic radiotherapy and to find out if changing the make-up of the gut flora in individual patients will be beneficial.

In the shorter term, we hope this study sheds some light on whether some patients with a particular make-up of bacteria respond differently to radiotherapy, which in turn could affect the amount of radiotherapy they are offered.”

Dr Miguel Reis Ferreira, Clinical Research Fellow at The Institute of Cancer Research, London, who designed and will manage the project, said:

“Radiotherapy is a vital part of treating cancers that form in the pelvis – including prostate, bowel and ovarian cancers. Its success is made clear by an increasing number of cancer survivors. But side-effects can be long-lasting and quite severe in some patients, so it’s crucial that we better understand how to minimise them.

“My interest in this area stems from a lecture I saw while undergoing PhD training at the Gulbenkian Institute of Science. This lecture brought intestinal bacteria – also known as the gut microbiota – and its importance for gut health to my attention. As a clinical oncologist under training, I became interested in its possible influence on GI side-effects after radiotherapy, which are still poorly understood. I came to London to undertake my research because the combined expertise of the ICR and The Royal Marsden, as well as our collaboration with colleagues at Imperial College will allow a globally unique set-up to explore this possibility.”

Dr Jervoise Andreyev, Consultant Gastroenterologist in Pelvic Radiation Disease at The Royal Marsden, who is co-leading the study, said:

“The idea that the bacteria that live in our bodies have a part to play in disease is not a new one – indeed the concept that changing the make-up of gut bacteria as an actual treatment predates antibiotics. Reports on the success of faecal transplants for infectious colitis, for example, were already available in the fifties. Recently, new technologies for identifying bacteria and understanding their function made the potential of microbiota come back to the forefront of biomedical sciences.

“This particular study follows on from previous pilot studies to come out of the wider work at our Gastrointestinal Unit, which is a world-leading centre not only for research, but mainly for the treatment of patients with GI symptoms after cancer treatment. It also pulls on the expertise in metabonomics of our partners at Imperial College London.”

The study

The patients will all be treated with radiotherapy in clinical trials performed at the Marsden, and split into three groups for separate arms of the new study. Some 60 patients will have stool, urine and blood samples taken over time as they progress through radiotherapy treatment. The stool samples will be analysed using a genetic technique known as 16S-based phylotyping, which allows researchers to know what species of bacteria are present in the gut. Differences in these species between healthy patients and patients with GI symptoms after radiotherapy may point out new mechanisms of this serious disease.

By looking at how metabolites change between people that have intestinal problems after radiotherapy and people that do not, researchers will also be able if these changes actually reflect differences in the microbiota. Gut bacteria produce important molecules such as short chain fatty acids or methane, which may be beneficial or harmful, so this will make clear if the microbiota is a potential culprit in this disease – either as a whole or because of the influence of specific species. In the longer term, the ultimate aim of the research programme will be to use this information to find ways of changing the make-up of gut bacteria to benefit patients.

A second arm of the study will look at 250 trial patients who are already being followed up after radiotherapy. As with the group of 60 patients followed over time, 16S analysis and metabolite information will be combined with information from patient questionnaires, which will detail the symptoms patients experience following radiotherapy.

The final arm of the study will compare 10 patients experiencing intestinal problems after radiotherapy with 10 patients who are not, but all of whom have extra bacterial samples taken from their intestine following routine endoscopy during cancer treatment. This final arm of the study will allow researchers to see if there are differences between stool samples and samples from the intestinal lining, called the mucosa. These researchers will thus have important, solid information that may pave the way for making radiotherapy an even more effective treatment in the future.