A recent study has revealed how Epstein-Barr virus (EBV) intensifies ulcerative colitis (UC), a debilitating inflammatory bowel disease. Researchers discovered that EBV infection triggers macrophage pyroptosis—a form of inflammatory cell death—by accelerating glycolysis, a key metabolic pathway. This cascade of events worsens colonic inflammation and disrupts the intestinal barrier, shedding new light on how viral infections contribute to UC. The findings not only deepen our understanding of UC pathogenesis but also open doors to novel treatments targeting EBV-driven inflammation.
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-1β (IL-1β), 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.
Dr. Hu Zhang, the study's corresponding author, underscored the importance of these discoveries: "Our research provides compelling evidence that EBV actively contributes to UC severity by triggering inflammatory cell death in macrophages. More significantly, we have identified glycolysis as a potential target for intervention. By disrupting this metabolic pathway, we may be able to curb EBV-driven inflammation and improve treatment outcomes for UC patients."
These findings could revolutionize UC treatment strategies. Current therapies primarily rely on immunosuppressants, which, while effective at controlling inflammation, may leave patients more vulnerable to viral infections like EBV. The study suggests that targeting glycolysis could offer a new therapeutic avenue—one that specifically combats EBV-induced inflammation while preserving immune function. Additionally, antiviral treatments that directly suppress EBV replication could be explored as adjunct therapies for UC patients with confirmed EBV infections. The next step will be clinical trials to translate these promising findings into real-world treatment strategies.
This research not only uncovers a hidden viral trigger in UC but also paves the way for innovative, precision-based therapies—offering new hope to patients struggling with the relentless burden of inflammatory bowel disease.
