Ulcerative colitis (UC) is a chronic, relapsing disease that causes painful inflammation and ulcers in the colon. While its exact causes remain elusive, mounting evidence suggests that viral infections, particularly Epstein-Barr virus (EBV), may worsen disease severity. Elevated EBV DNA and RNA levels have been detected in the colonic tissues of UC patients, correlating with more aggressive symptoms, higher risks of surgery, and poorer treatment responses. However, the precise mechanisms linking EBV to UC progression have remained a mystery. Given these challenges, scientists have been eager to unravel how EBV contributes to UC and explore new therapeutic strategies.
In a pivotal study (DOI: 10.1093/pcmedi/pbaf002) published on January 21, 2025, in Precision Clinical Medicine, researchers from West China Hospital, Sichuan University, investigated the role of EBV in UC. By analyzing tissue samples from UC patients and conducting experiments in mouse models infected with murine gamma-herpesvirus 68 (MHV-68)—a close relative of EBV—the team uncovered a critical connection between EBV infection and macrophage-driven inflammation. Their results highlight a previously unknown mechanism that amplifies UC symptoms.
The study revealed that EBV infection dramatically increases the levels of pyroptosis-related proteins, including Gasdermin D, NLRP3, interleukin-1? (IL-1?), and interleukin-18 (IL-18), in the colon. Macrophages infected with EBV exhibited excessive inflammatory responses, leading to severe intestinal damage and compromised gut integrity. Notably, the researchers identified glycolysis as a central driver of this process—fueling the inflammation that worsens UC. Importantly, when the team blocked glycolysis using the metabolic inhibitor 2-deoxy-D-glucose (2-DG), macrophage pyroptosis was significantly reduced, leading to decreased inflammation in the colitis-afflicted mice. These findings establish a direct link between EBV, metabolic dysregulation, and immune activation in UC.
