Scientists Discover New Enzyme in Gut Bacteria That Contributes to Pain Signaling

Research has focused on finding targeted treatments for abdominal pain associated with digestive disorders. The latest studies have identified a bacterial enzyme that regulates the activity of a pain receptor in the gut, opening up new avenues for treating gut pain. Using nanoparticles, scientists have successfully delivered a drug to cells to block the pain receptor, providing a promising approach for treating abdominal pain.

Key Takeaways:

• Researchers at NYU College of Dentistry and Stanford University School of Medicine discovered a new bacterial enzyme, produced by Bacteroides fragilis (B. fragilis), that cleaves and activates the pain receptor PAR2.
• The enzyme was found to be responsible for triggering pain, inflammation, and intestinal barrier disruption in cells and mice.
• The researchers used nanoparticles to deliver a drug that blocks PAR2, demonstrating a precision-targeted approach to treating abdominal pain.
• The studies provide evidence of the role of proteases in the pathway between gut bacteria and the host, offering implications for understanding the triggers of symptoms in inflammatory bowel disease.
• The research was supported by the National Institutes of Health, Takeda Pharmaceuticals, the Deutsche Forschungsgemeinschaft, and Stanford University.

Statistics:

• More than 50 human strains of bacteria in the gut were tested, and over 50 produced enzymes that cleaved and activated PAR2.
• The researchers honed in on B. fragilis, a normally non-pathogenic bacterium that can produce a robust protease that activates PAR2.
• In cellular studies, the nanoparticle-delivered drug was found to be 10 times more effective at inhibiting signaling of PAR2 compared to the drug on its own.
• In studies of mice with inflammatory bowel disease, giving the mice nanoparticles containing the drug diminished pain-like behaviors.

Sources:

• Nigel Bunnett, Professor and Chair of the Department of Molecular Pathobiology, NYU College of Dentistry, and Nigel Bunnett, Faculty Member, NYU Pain Research Center.
• Matthew Bogyo, Professor of Pathology, Microbiology, and Immunology, Stanford University School of Medicine.
• Cell Host & Microbe (2022) - "A Prokaryotic Protease Regulates Gut Pain through the Cleavage of a Pain Receptor".
• Proceedings of the National Academy of Sciences (PNAS) (2023) - "Nanoparticle-mediated delivery of a PAR2-targeting drug for the treatment of abdominal pain".
• National Institutes of Health (R01 DK130293, R01 NS125413, 1S10OD030473)
• Deutsche Forschungsgemeinschaft
• Stanford University
• Takeda Pharmaceuticals