Breakthrough in Sepsis Prevention: New Pathway Identified by Researchers

Researchers at the University of Saskatchewan have uncovered a promising new approach to defending the body against sepsis, a severe and often deadly condition resulting from an abnormal immune response to infection. Sepsis remains the leading cause of death in intensive care units worldwide and poses significant challenges for medical professionals.

Dr. Scott Widenmaier, an associate professor in the Department of Anatomy, Physiology and Pharmacology, focused on a specific protein that could be key to enhancing the body's natural defenses. His team’s recent study, published in ellular and Molecular Gastroenterology and Hepatology,xplores how manipulating this protein may improve disease tolerance.

Sepsis is characterized by the immune system's overreaction, releasing cytokines and other factors intended to eradicate pathogens but often resulting in damage to vital organs like the heart, kidneys, and liver. This dysregulated response can lead to organ failure and death. Widenmaier explains that many believe infection is caused directly by bacteria or viruses; however, the critical factor is the body's immune response that can become harmful.

Traditional treatments target the infection itself, but recent research emphasizes harnessing the body's innate ability to tolerate disease. The team identified a transcription factor in the liver called NRF1, which acts as a molecular switch to activate disease tolerance mechanisms. In experimental models infected with E. coli, increasing NRF1 levels led to enhanced responses and protection against sepsis. Overexpressing NRF1 boosts the secretion of very low-density lipoprotein (VLDL), a particle that helps safeguard organs from damage caused by sepsis.

Looking ahead, Widenmaier and his colleagues aim to explore ways to pharmacologically or genetically target NRF1 to augment health outcomes. Although these findings are still in the early research phase and not yet tested in humans, they offer a promising new avenue for sepsis treatment. The team’s ongoing efforts aim to bridge the gap between laboratory research and clinical applications, seeking innovative strategies to reduce sepsis-related mortality.

This research highlights the potential of targeting internal mechanisms of disease tolerance, which could revolutionize future sepsis management and improve patient survival rates.

source: https://medicalxpress.com/news/2025-09-method-sepsis.html