Gut cell atlas reveals gene activity changes in Crohn's disease

A gut cell atlas built from patient biopsies reveals gene activity changes across gut cell types in Crohn's disease.  

In one of the largest investigations of its kind, researchers from the Wellcome Sanger Institute in Hinxton, near Cambridge, and collaborating institutions analysed more than 1.1 million gut cells from healthy people and people with Crohn's disease, a chronic inflammatory bowel condition. Comparing cell types, gene expression, and cellular pathways, the researchers created a detailed cellular map known as the 'IBDverse'.

'By creating this unprecedented map of more than one million gut cells, we are giving researchers around the world a powerful new tool to uncover how inflammation begins, persists and may one day be stopped' said Dr Monika Krzak, from the University of Cambridge and co-first author of the study published in Nature Genetics.

Biopsies of the terminal ileum, a section of the intestine commonly affected by Crohn's disease, were collected from 111 people with the condition and 232 unaffected people who represented a control group. The samples were analysed using single-cell RNA sequencing technology, a technique that measures RNA activity in individual cells and allows researchers to link gene expression patterns to specific cell types.

The researchers identified a distinct Crohn's disease signature, characterised by changes in immune cell populations and altered gene activity across multiple cell types. They also observed increased expression of immune-related genes in intestinal progenitor cells, which give rise to specialised cells in the gut. The authors suggest that these changes may persist even after inflammation has resolved, potentially contributing to ongoing disease processes.

In addition, people with Crohn's disease had an increased number of inflammatory macrophages expressing the ITGA4 gene and pro-inflammatory cytokines. These findings highlight cellular pathways that may contribute to disease development and could help researchers identify potential therapeutic targets for future investigation.

This work complements another study recently published in Nature that used the IBDverse resource to investigate how inherited genetic risk factors for inflammatory bowel disease affect specific cell types. Together, these two studies provide insights into both the genetic factors of inflammatory bowel disease and the cellular changes linked to Crohn's disease.

By supporting future research, public databases such as IBDverse are '…the kind of open science that can accelerate discoveries and bring us closer to better treatments for patients,' said Dr Krzak.