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April 03, 2025
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‘Distinct viral exposure patterns’ found in patients with Crohn’s years before diagnosis

Key takeaways:

  • Patients with Crohn’s disease had increased exposure to Epstein–Barr virus 5 to 7 years before diagnosis vs. healthy controls.
  • Patients infected with Epstein–Barr virus were 3.05-times more likely to develop CD.

Patients with Crohn’s disease had high Epstein-Barr virus seropositivity in the preclinical period and at diagnosis of inflammatory bowel disease, according to results of a cohort study of military personnel published in Gastroenterology.

“The sharp increase in IBD incidence over the past 50 years suggests a significant role for environmental contributors beyond genetic factors,” Anubhab Nandy, PhD, researcher in the division of gastroenterology, hepatology and nutrition in the department of pediatrics at Boston Children’s Hospital and Harvard Medical School, told Healio.

Anubhab Nandy, PhD

“While the microbiota’s involvement in IBD has been widely studied, research has primarily focused on bacterial alterations, with limited attention to the role of viruses,” he continued. “Moreover, previous cross-sectional studies were confounded by factors, such as ongoing IBD treatment and inflammation, which may impact microbial detection. To establish a clearer causal link between viral exposures and IBD pathogenesis, we felt a preclinical, subject-based unbiased approach was necessary.”

Nandy and colleagues screened serum samples of individuals in the PREDICTS study, a cohort of healthy active component military personnel, for antiviral antibodies using VirScan (CDI Labs).

According to study results, patients with CD had increased exposure to herpesvirus 4, or Epstein-Barr virus (EPV), 5 to 7 years before diagnosis compared with healthy controls (P = .02).

Results additionally showed that individuals infected with EBV during this time were 3.05-times more likely to develop CD (HR = 3.05; 95% CI, 1.28-7.22).

“We identified distinct viral exposure patterns in IBD, both at the preclinical stage and at diagnosis, with Crohn’s disease and ulcerative colitis exhibiting significantly different profiles,” Nandy said.

Serological validation confirmed a higher prevalence of anti-EBV antibodies among patients with CD who had increased EBV exposure before diagnosis, according to Nandy.

Risk-estimation analyses further indicated that EBV infection increases susceptibility to Crohn’s disease development,” he said. “However, this association was absent in a separate cohort of younger at-risk individuals, suggesting that EBV’s role in Crohn’s disease may be influenced by factors such as age and population distribution. It was unexpected to observe significantly high EBV exposure in prospective Crohn’s disease patients, years before disease diagnosis.”

Nandy further noted that despite the observation of EBV in patients with IBD, “it has always been a conundrum whether EBV is associated with IBD pathogenesis, or simply a bystander effect of ongoing inflammation and IBD medications.”

“We are actively investigating the mechanisms through which EBV may contribute to IBD pathogenesis,” he said. “In collaboration with multiple research groups, we are analyzing EBV infection across diverse IBD cohorts while integrating patient data on disease progression, complications and multiomics parameters, including cytokine profiles and gene expression data. These studies aim to clarify the link between EBV infection and IBD, offering critical insights into disease mechanisms and potential therapeutic targets.”

For more information:

Anubhab Nandy, PhD, can be reached at anubhab.nandy@childrens.harvard.edu.