AI-Powered Research Uncovers Genetic Link to Crohn’s Disease & Reveals Macrophage roles in Gut Health
Researchers at the University of california, San Diego, have utilized machine learning to pinpoint a crucial genetic connection to Crohn’s disease adn illuminate the role of immune cells called macrophages in maintaining gut health. The study identified 53 genes that contribute to macrophage status in Inflammatory Bowel Disease (IBD), offering new insights into the molecular pathways underlying gut homeostasis and disease progression.
Macrophages, described by UC San Diego’s gajanan Katkar as “the peacekeepers” of the gut, normally exist in two states: an inflammatory state for fighting infection and a non-inflammatory state for repairing damage. A healthy gut relies on a balance between these states. The research team monitored gene expression in these immune cells to determine which contribute to gut health and which drive inflammation.
The study focused on the NOD2 protein, known to be involved in preventing IBD, but whose precise function in the condition’s development was previously unclear. Experiments conducted on lab-grown cells and samples from healthy individuals and those with Crohn’s disease revealed that mutations disrupt the normal protective mechanisms of NOD2.
Crucially,the research highlighted the cooperative relationship between NOD2 and a protein called Girdin.Girdin, produced by a specific gene, supports the non-inflammatory macrophage state. “NOD2 functions as the body’s infection surveillance system,” explains cell scientist Pradipta Ghosh at UC San Diego. “When bound to girdin, it detects invading pathogens and maintains gut immune balance by swiftly neutralising them. Without this partnership, the NOD2 surveillance system collapses.”
Without both NOD2 and Girdin, macrophages become excessively inflammatory in attack mode and less effective at repairing damage. The findings shed light on how this breakdown contributes to the development of Crohn’s disease.
Understanding Crohn’s Disease:
Crohn’s disease is a long-term condition causing inflammation in parts of the digestive system. Symptoms include stomach pain, diarrhea, weight loss, and tiredness. While there is currently no cure, treatment focuses on controlling symptoms through medication to reduce inflammation, dietary changes, and, in severe cases, surgery.
