Identifying a novel diagnostic test to predict clinical response to treatment with biological drugs in Crohn’s disease patients.

Background:

Crohn’s disease (CD) is a chronic relapsing incurable inflammatory bowel disease (IBD) affecting approximately 165/100000 people in the UK. The cytokine milieu in the intestine is an important factor in the maintenance of the immune balance, and in gut inflammation, this balance is dysregulated resulting in mucosal inflammation.  The gastrointestinal tract interacts with a huge variety of diverse microbiota. Changes in the diversity of this microbiota (dysbiosis) is associated with changes in the cytokine profile and considered to be an important factor in the aetiology of CD.

Monoclonal antibody therapy has revolutionised the treatment of IBD. However, many patients do not respond to the drugs and some develop serious side effects and/or recurrence after the treatment is discontinued. Furthermore, information on the effect of biological drugs on the bacterial composition in relation to the systemic cytokine profile in CD is still unknown.

Hypothesis:

Dysbiosis in CD correlates with systemic changes in the production of pro- and anti-inflammatory cytokine.

Aims:

To characterise dysbiosis in CD and examine concurrent changes in gut bacteria and serum cytokine profiles in response to treatment with biological drugs including vedolizumab and infliximab.

Research Plan:

Pro- and anti-inflammatory cytokines, immune cell phenotype and activation will be assessed by flow cytometry on serum and blood immune cell samples obtained from CD patients.  Bacterial DNA will be extracted from stool samples and dysbiosis of gut microbiota will be assessed before and after biological treatment using Luminex technology and GA-map Dysbiosis Test. 

Advanced statistics and bioinformatics will be used to determine the relation between the cytokine levels and dysbiosis.

Outcome:

The data obtained will potentially help predict patient response to biological drugs and will bring closer the notion of personalised medicine.

For further information regarding the project or an informal discussion please contact Director of Studies, Dr Hafid Omar  h.omar6@wlv.ac.uk