Key Gene Identified That Protects Against Irritable Bowel Disease

Investigators recently identified the gene Gatm, which protects the body against inflammatory bowel disease (IBD) by rapidly replenishing the intestinal mucosal barrier.

Normally, the intestines are lined with mucus to form a barrier “similar to a demilitarized zone,” according to the investigators. The barrier protects the intestinal walls from bacteria, both good and bad. However, if bacteria permeates the mucus layer and reaches the intestinal walls, inflammation will occur.

In a study published in the Proceedings of the National Academy of Sciences, the authors found a mutation in the Gatm gene. They then used the CRISPR/Cas9 gene editing technology to confirm the link.

The investigators used mice with 2 copies of the recessive Gatm mutation, which mimicked IBD symptoms found in humans. Mice who received creatine in their drinking water experienced improvement in their symptoms

“The Gatm gene is needed for the synthesis of creatine, a substance made in the liver that travels to the barrier cells and allows them to utilize energy in an efficient manner,” said senior author Dr Bruce Beutler.

“Mutations in this gene and others needed for mobilization of energy in cells may account for some cases of IBD in humans. IBD is a chronic, relapsing-remitting disease in which evidence of healing in the lining of the digestive tract is critical for long-term remission.

“Current therapy tends to focus on reducing the inflammatory response. However, proper healing of the mucosal layer and cells that line the digestive tract is essential in long-term remission. This study indicates that health requires effective energy metabolism. Knowing these genes may help us to understand how IBD occurs in humans, and how to treat it.”

Several other potential colitis genes were also identified, according to the investigators. Each gene was found by random germline mutagenesis.

The findings indicate the necessity of creatine for providing the energy required for rapid replenishment of the mucosal barrier, the authors concluded.