According to a recent study, to fight against intestinal inflammation linked to inflammatory bowel diseases (IBD), an effective strategy could be to block a new target: microRNAs. Explanations.
An article to be found in the magazineInserm n°63
Abdominal pain, recurrent diarrhea, chronic fatigue…: chronic inflammatory bowel diseases, abbreviated IBD, including Crohn’s disease and ulcerative colitis, can literally ruin life. They are linked to chronic inflammation of the intestine, an exaggerated and persistent immune reaction, harmful in the long term. Although they affect more than 200,000 French people, including 10% children, and are associated with an increased risk of colon cancer, these pathologies remain incurable. Certain medications help reduce intestinal inflammation. Problem: 20 to 50% of patients become resistant to it over time. But the good news is that Émilie Viennois and her colleagues at the Inflammation Research Center in Paris have highlighted a new therapeutic target: microRNAs present in large quantities in the intestine.
Discovered in 1993, microRNAs belong to the same family of molecules as messenger RNAs (mRNA), famous for having made it possible to obtain the first anti-Covid vaccines. But they are much smaller with a maximum of 22 nucleotidescompared to 200 to 15,000 for mRNAs. Furthermore, they are not translated into protein, but regulate gene expression.
Direct action on the microbiota
During their work, the Inserm researcher and her team noted that two microRNAs were present in high quantities in the stools of people and mice suffering from intestinal inflammation: let-7b and miR-21. The scientists therefore administered these two molecules to mice not predisposed to developing intestinal inflammation. And they observed several disturbances typical of intestinal inflammation, including an increase, in the large intestine, in the production of several molecules secreted in the event of inflammation and a modification in the composition of the intestinal microbiota.
Through experiments in mice lacking intestinal microbiota and on cultures of human microbiota, the team then elucidated the mechanism of action of let-7b and miR-21. “ Our results indicate that these two fecal microRNAs act directly on the microbiota. And it is the disruption of the latter that contributes to intestinal inflammation », explains Émilie Viennois.
-Finally, the scientists attempted to block both microRNAs using molecules designed for this purpose. And bingo: the administration of these inhibitors to mice predisposed to developing intestinal inflammation prevented the increase in the production of several inflammatory molecules. Better still, the 80-day survival rate of rodents increased by 25 to 40%, depending on the inhibitor used. “ In July 2024, we filed an international patent to protect this new treatment concept for chronic inflammatory bowel diseases », underlines Émilie Viennois. It now remains to be verified that blocking miR-21 and let-7b can do better than existing anti-inflammatories.
Émilie Viennois is a researcher at the Inflammation Research Center in Paris (CRI, unit 1149 Inserm/Université Paris-Cité).
Source : M. Casado-Bedmar et al. Fecal let-7b and miR-21 directly modulate the intestinal microbiota, driving chronic inflammation. Gut microbes.September 3, 2024; doi:10.1080/19490976.2024.2394249
Author: K.B.
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