Study Discovers Gene That Protects Against Inflammatory Bowel Disease

The researchers at UT Southwestern Medical Center have identified a gene that helps to protect the gut against inflammatory bowel disease (IBD). The study conducted on mice found a mutation in the Gatm gene and used CRISPR/Cas9 gene-editing technology to confirm the link.

The researchers noted that the Gatm gene is necessary for the rapid replacement of the intestinal mucosal barrier that protects the intestinal wall from inflammation caused by bacteria in the digestive tract. "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," senior author and director of UT Southwestern Center for the Genetics of Host Defense, Dr. Bruce Beutler said.

IBD is characterized by a chronic, recurring immune response and inflammation of the gastrointestinal tract, with the two most common IBD been Crohn's disease and ulcerative colitis as acknowledged by the Centers for Disease Control and Prevention (CDC). While the Crohn's disease is described as a condition that can affect any part of the digestive tract, ulcerative colitis is only limited to the large intestine, according to Esciencenews.

The body normally maintains a balance between the ability of the intestinal tract to respond to bacteria that causes disease, and tolerance of good bacteria that aid digestion. The researchers said to better understand the mucosal barrier, the intestines should be compared to a battlefield during a lull in fighting.

In normal conditions, mucus lines the intestines forms a barrier similar to a demilitarized zone, which protects the intestinal walls from both disease-causing and beneficial bacteria. However, inflammation is the result if the bacteria succeeds in penetrating the mucus layer and thus, have access to the intestinal walls, the researchers explained.  

In the study, the researchers found that mice with two copies of the recessive Gatm mutation displayed symptoms that are similar to that of people with IBD such as weight loss, diarrhea, and death of cells lining the intestine. They discovered that the symptoms subsided when the mice were administered creatine via their drinking water.

The findings of the study reveal that creatine is necessary to supplement the energy needed for the rapid replacement of the mucosal barrier. Beutler stated that mutations in this gene and others necessary for mobilization of energy in cells may account for some cases of IBD in humans.

He continued to say that the experiment identified several other potential colitis genes, but the effect of this particular one on the barrier cells' energy requirements suggests a new category of mutations with the potential to cause IBD. The researchers found each gene by random germline mutagenesis, in other words, mutations were developed in order to study resulting traits.

The condition is a chronic, relapsing, remitting disease in which evidence of healing in the lining of the digestive tract is critical for long-term remission. The treatment currently used to remedy the condition focuses on decreasing the inflammatory response. The researchers believe that proper healing of the mucosal layer and cells that line the digestive tract is necessary for long-term remission. Their findings suggest that proper healing requires effective energy metabolism, according to Science Daily.

They believe that knowing these genes better may assist researchers and scientist to understand how IBD occurs in humans and how to prevent and treat it. The researchers published the findings in the Proceedings of the National Academy of Sciences.