Researchers have uncovered what drives the development of scar tissue in the intestines of people with Crohn’s disease.

The study, led by researchers at the Institute of Genetics and Cancer, found clusters of immune cells in the gut which may be stimulating nearby cells to generate excess scar tissue, known as fibrosis.

The discovery could help pinpoint new therapeutic targets to prevent or slow the development of fibrosis, a serious complication of Crohn’s disease.

Crohn’s disease is a chronic inflammatory condition affecting the digestive tract. Over time, ongoing inflammation can lead to fibrosis, where excess collagen builds up in the bowel wall. This scarring can cause the intestine to narrow and become blocked, requiring surgery.

Despite affecting one in five patients with Crohn’s disease, the biological processes that trigger fibrosis remain poorly understood. Current treatments primarily target inflammation rather than the scarring itself.

The research team analysed intestinal tissue samples from Crohn’s disease patients with fibrosis, focusing on the ileum – the final part of the small intestine where the disease most commonly develops.

They used archived intestinal tissue samples to examine structural changes across the different layers of the bowel wall.

They found significantly increased fibrosis and immune cell infiltration in Crohn’s disease tissue compared with normal tissue. The submucosa – a deeper layer of the bowel wall – had particularly high levels of scarring, indicating it may play an important role in the early stages of fibrosis.

Researchers next analysed fresh intestinal tissue samples using a cutting-edge technique to study gene activity in individual cells, known as single-cell RNA sequencing.

They identified a link between clusters of immune cells – known as Crohn’s lymphoid aggregates – and groups of endothelial cells, which normally line blood vessels. The endothelial cells appeared to form distinctive structures surrounding the Crohn’s lymphoid aggregates.

Further analysis revealed signalling interactions between these clusters and nearby cells responsible for producing collagen, suggesting that they may actively promote fibrosis.

Our findings highlight previously unrecognised interactions between immune cells, endothelial cells and collagen-producing cells in Crohn’s disease. By combining traditional pathology with single-cell transcriptomics, we were able to confirm these changes using two independent approaches and uncover biological signalling pathways that may provide new therapeutic targets. – Dr Michael GlinkaPostdoctoral Research Fellow

Pathologists, gastroenterologists, biomedical scientists and computer experts at the University of Edinburgh and Heriot-Watt University in Edinburgh worked together with researchers in genomics and transcriptomics at the Earlham Institute and Sanger Institute for over six years, to study the cellular and molecular mechanisms of the process of fibrosis in Crohn’s Disease, in order to identify new therapeutic targets that can be used to treat patients to try to slow down or reverse fibrosis. –  Professor Mark ArendsProfessor of Pathology and Head of Edinburgh Pathology, University of Edinburgh

The research highlights potential therapeutic targets that could be explored to interrupt the scarring process and develop treatments specifically aimed at fibrosis in Crohn’s disease.

Fibrosis remains one of the most challenging complications of Crohn’s disease because current treatments primarily target inflammation rather than the scarring itself. Understanding the cellular signalling pathways that link immune activity to collagen production could help guide the development of therapies aimed at preventing or slowing fibrosis. –  Dr Shahida DinConsultant Gastroenterologist and Research Clinician at NHS Lothian

Source – The University of Edinburgh