Artificial intelligence has resolved a quarter-century-old scientific controversy about Crohn's disease
With the help of artificial intelligence, scientists have discovered how a key gene triggers Crohn's disease, a mystery that has lasted for more than 25 years, writes News.ro.
A discovery by researchers at the University of California in San Diego explains the genetic mechanism that causes severe intestinal inflammation. The team has resolved a scientific controversy that has persisted for a quarter of a century regarding the first genes associated with an increased risk of developing Crohn's disease, a severe form of inflammatory bowel disease.
The human digestive system is protected by two main types of macrophages, specialized immune cells that patrol the gut.
Some act as “warriors”, destroying dangerous microorganisms, while others function as “healers”, repairing damaged tissues.
When the balance between these two roles is disturbed, chronic inflammation, abdominal pain and intestinal lesions characteristic of Crohn's disease occur.
Artificial intelligence, used to understand cells
Researchers at the University of California, San Diego School of Medicine combined artificial intelligence with molecular biology to understand what causes a macrophage cell to become aggressive or healing.
The study also provides an explanation for how the NOD2 gene, the first discovered to be involved in the risk of Crohn's disease, influences the behavior of the intestinal immune system.
Using a machine learning algorithm, the team analyzed thousands of gene expression patterns of macrophages taken from intestinal tissues affected by inflammatory bowel disease and from healthy tissues.
They identified a “genetic signature” consisting of 53 genes that separates inflammatory macrophages from those involved in tissue regeneration.
One of these genes codes for a protein called girdin (GIV).
The researchers found that, in non-inflammatory macrophages, a specific region of the NOD2 protein binds to girdin, which helps suppress excessive inflammation, eliminate harmful microbes, and repair intestinal tissue.
Confirmation of the hypothesis
But the most common mutation in the NOD2 gene, associated with Crohn's disease, deletes exactly this link, which causes a dangerous imbalance between inflammatory and healing macrophages.
Professor Pradipta Ghosh, lead author of the study, explained that “NOD2 functions as an infection surveillance system in the gut. When it binds to girdin, it quickly recognizes pathogens and maintains the immune balance. Without this partnership, the system collapses.”
To confirm the hypothesis, the researchers tested the effects of the absence of the girdin protein on mouse models. Animals without this protein showed an imbalance of intestinal flora, severe inflammation of the small intestine and, in many cases, died of sepsis, a fatal systemic reaction to infection.
“The gut is a true battlefield, and macrophages are the peacekeepers. AI has allowed us, for the first time, to clearly identify the camps involved in this microscopic battle,” explained Dr. Gajanan Katkar, co-author of the study.
The result, useful for new therapies
By combining artificial intelligence, mechanistic biochemistry and animal models, the University of California team managed to clarify one of the longest-running disputes in Crohn's disease research.
The results could contribute to the development of therapies that restore the lost interaction between NOD2 and girdin, opening new directions for the treatment of inflammatory bowel diseases.
The study was carried out by researchers from the Faculty of Medicine of the University of California, San Diego and published this month in the scientific journal Cell Reports.
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