A multimodal evaluation of severe cutaneous and anogenital Crohn's disease.

Summary

Crohn’s disease (CD) is associated with genetic alterations and changes in the types of bacteria found in the gut - our microbiome. These changes lead to inflammation and reduce the ability to heal well. Over a quarter of people living with Crohn’s will have a form of the condition that affects the gut and the skin around the back passage (perianal Crohn’s disease). This can cause many symptoms including pain, foul discharge and incontinence and can also have a huge impact on people’s sex life and mental health.

Our research involves people with an extremely aggressive form of perianal Crohn’s disease resulting in the need for major surgery to remove the rectum and back passage. We propose that genetic variations cause changes in the lining of the gut and skin of these patients. This in turn drives a change in the types of bacteria present in the gut and skin, leading to uncontrolled inflammation and poor healing. Our previous research, in mice, has shown that specific genetic mutations known to be associated with Crohn’s disease are associated with a change in skin bacteria leading to delayed wound healing.

This project aims to identify the genetic and clinical factors that are associated with people that develop this severe form of CD. The NIHR IBD BioResource provides a unique opportunity to investigate this in a much larger group of patients than could be studied from a single centre. The second aim is to study how these genetic changes may cause the bacteria on the skin and gut to drive the severe inflammation seen in these people. This work will help to identify those at higher risk of having severe disease, providing better prognostic information and ultimately improve the care provided to these people.