Multi-omics approaches to understand inflammatory bowel disease
Multi-omics approaches to understand inflammatory bowel disease
Inflammatory bowel disease (IBD) is a condition that causes long-lasting, recurring inflammation in the intestine. The exact cause of IBD is still unknown, but research shows it likely results from a combination of genetics, environmental factors, and the community of bacteria living in the gut (the gut microbiome).
In this thesis of Iwan Hidding, we studied the gut microbiome in children who were newly diagnosed with IBD. We found that their microbiome already showed patterns associated with disease at the time of diagnosis, compared with healthy children and children with other intestinal problems such as polyps.
We also studied people with Lynch syndrome, a hereditary condition that greatly increases the risk of developing cancer, particularly colorectal cancer. These individuals had a gut microbiome that was distrinct from that of the general population. However, these differences could not be used to predict whether intestinal lesions were present.
Next, we investigated somatic mutations in intestinal tissue from people with IBD. Somatic mutations are genetic changes that accumulate locally in cells during a person’s life and are different from the genetic variants they are born with. We found that these mutations frequently occurred in genes known to cause very-early-onset IBD and primary immune deficiencies. This suggests that such mutations may contribute to the development or progression of adolescent or adult onset IBD.
Finally, we studied how genetics, environment, diet, and the gut microbiome together relate to IBD in the general population. The results indicate that a person’s genetic predisposition and their gut microbiome are the strongest factors associated with the disease.