IBD-RESPONSE: Defining microbial predictors of responsiveness to biological therapies in Crohn's disease and ulcerative colitis

Crohn's disease and ulcerative colitis (UC) are types of a bowel condition known as inflammatory bowel disease (IBD) and the symptoms (diarrhoea, pain, fatigue) have a major impact on daily life. IBD affects around 1 in 125 people in the UK and this is expected to rise to 1 in 100 by 2028. "Biologicals" are powerful medications that are given to reduce inflammation in IBD.

These treatments can be effective but up to 40% of patients don't respond, and in those that do, many don't respond well enough to stay on the drug after one year of treatment. Unfortunately, we have no way to predict which patients are most likely to benefit from treatment (known as responders), and we do not fully understand how medications work in responders.

As these drugs may have serious side effects and are expensive to the UK healthcare system, this lack of understanding is a major obstacle in deciding which treatment is best to give to an individual patient, and when to give it to them in order to have the greatest benefit and the least risk.

Recent data from small studies in people with IBD and larger studies of people with cancer, show that certain bacteria in stool (faeces) may predict who will respond or fail to respond to treatments. In animal studies, changing the number and type of these bacteria can influence treatment outcomes. These studies strongly suggest the number and types of certain bacteria may predict which patients do and do not respond to IBD treatment.

However, these studies used different techniques in varied groups of patients and were too small to give a definite answer, Nonetheless, they do suggest that if a large enough group of patients were studied it should be possible to identify which specific bacteria are important for understanding treatment response in IBD, and what the function of these bacteria are.

We are a group of researchers with a world-leading track record in clinical, bacterial, immune and genetic research. For the last 5-years we have successfully recruited 27,500 patients into a research study called the IBD Bioresource to study the human genes involved in the development or behaviour of IBD. We now seek funds to begin a separate study focussing on gut bacteria called IBD-RESPONSE.

This study will benefit from the knowledge and facilities we already have from the IBD Bioresource. We will recruit 1,125 patients starting biological therapy in IBD as part of routine NHS care from 30 centres across the UK. We will collect stool, and where possible intestinal biopsies during routine endoscopy (camera into the gut), to study the gut bacteria before, and during, these treatments.

By using state-of-the-art machinery and cutting-edge computer analysis techniques we will identify these microbes, study their function, and examine how microbes may interact with the human immune system. The outcome of our study will be to develop a tool that predicts which patients are likely or unlikely to respond to the different treatment options in IBD.

We will create the largest collection (biobank) in the world of stool and intestinal tissue specimens, at multiple timepoints and with detailed clinical information, from this important group of patients that will be open to other researchers to use in the future.

By creating a predictive tool for response to treatment, IBD-RESPONSE will lead to clinical trials that can shape future treatment pathways in IBD. This may be by allowing the development of a test (biomarker) to help healthcare professionals decide which treatment is best suited to an individual patient, or to identify which bacteria in the intestine could be targeted (either to reduce or increase presence) in order to improve treatment outcomes for patients.

This has the potential to improve quality of life, reduce patient risk and reduce unnecessary expenditure on ineffective treatments by the NHS for this debilitating disease.