Exploring IBD Treatment Through The Microbiome Lens

Jun, 2023 - by CMI

IBDs including Crohn's disease and ulcerative colitis may be treated with a two-drug combination that blocks both IL-22 and IL-1R, according to new microbiome-based data.

The investigation team looked at the microbial interactions with intestinal cells' "upstream signals." According to their findings, IL-22 and IL-1R can set off a "chain reaction" that results in an exaggerated inflammatory response. "The harmful function performed by IL-22 in the inflammatory response was previously unclear due to its synergistic effect with IL-1R signaling," stated corresponding author Chandrashekhar Pasare, Ph.D., DVM, of Cincinnati Children's. Director of the Center for Tolerance and Inflammation.

In the United States alone, it is estimated that 3 million individuals suffer from IBD. In 2017, there were 6.8 million cases globally, according to a global survey that was published in The Lancet. The IBD market was worth over $20 billion globally in 2017. There are now over 3,000 clinical studies being conducted for this illness. 

The study team investigated how immune cells in the intestinal mucosa identify and react to bacteria as well as communicate vital information to intestinal epithelial cells. According to them, a healthy signaling network between immune and epithelial cells enables the immune system to coexist peacefully with the gut's beneficial microorganisms.

The immune system may underreact or overreact when microbial-cell signals are altered by other factors, such as genetic changes or damage to the intestinal epithelium, which results in IBD. 

This study suggests that the immune cells in the stomach can identify microorganisms. The IL-1 protein is signaled by these immune cells, which raises the amount of the IL-22 protein. The IL-1 receptor (IL-1R), which is found on intestinal epithelial cells, is first activated by this protein in conjunction with IL-1. In addition to other genes that attract inflammatory cells to tissues, activation of the IL-1R also causes the activity of ROS genes. According to researchers, this cascade of events sets off an overactive inflammatory response that may harm the stomach.