French researchers have identified a distinct circulating viral community in patients with Crohn’s disease (CD) that may serve as a disease signature. The findings published in Gastroenterology challenge the long-held assumption that blood is sterile and suggest that alterations in the circulating virome may reflect intestinal barrier dysfunction in CD.

If confirmed in larger cohorts, these results could open a new avenue for biomarker development in inflammatory bowel disease.

Intestinal Barrier Dysfunction

To establish a more precise signature of CD beyond the analysis of intestinal microbiota, researchers from the INRAE: France’s National Research Institute for Agriculture, Food and Environment, Assistance Publique – Hôpitaux de Paris, Saint Antoine Hospital, Paris, France, focused on blood-borne microorganisms, particularly bacteriophages, which are viruses that infect bacteria.

Researchers have hypothesized that these microorganisms might be altered in the blood of individuals with CD because of intestinal barrier dysfunction and increased permeability.

To assess this hypothesis, the researchers analyzed blood samples from 15 patients with CD and 14 healthy individuals. A key finding was the clear presence of blood virome in both patient groups. Viruses have been detected in healthy individuals, although the blood has historically been considered sterile.

The blood virome was small in both groups, with approximately 100,000 viral particles per milliliter of plasma, compared with the intestinal virome, which reached approximately 1 billion viral particles per gram of feces.

Bacteriophages were the predominant components of the virome in both groups, with a mean of approximately 150 species per individual. Human viruses are rare and consist mainly of anelloviruses, which are generally considered nonpathogenic.

Distinct Phage Profiles

The second finding was that healthy individuals and patients with CD differed in terms of the bacteriophage species detected in their blood.

Several bacteriophages infecting bacteria of the genus Acinetobacter were identified in healthy individuals but were almost entirely absent in individuals with CD.

Conversely, multiple phages that infect bacterial species typically found in the intestine were detected exclusively in the blood of patients with CD. This observation may reflect the translocation of viruses from the intestinal microbiota into the bloodstream because of the increased intestinal permeability associated with the disease.

These results demonstrate the presence of a blood virome in all individuals and, for the “first time, suggest that the blood viral community has potential as a marker of CD,” wrote the authors.

This study had several limitations. “First, the cohort was relatively small. Although this limited number was sufficient to highlight CD-specific features, a larger validation cohort would be required to consolidate the results. Second, patients in our cohort are both in remission and in flare. Although comparisons between both states revealed no difference in our analyses, sample size remains small, and more homogenous groups with matching disease states may allow refinement of the present conclusions. Finally, our results suggesting an increased transfer of viruses from the intestine to the blood in patients with CD are based on metagenomics approaches only, and we are presently complementing them with cellular biology approaches,” wrote the authors.

Beyond identifying a distinct blood viral community in CD that could serve as a disease signature, these findings open new research avenues. These include studying bacteriophage passage across the intestinal barrier, analyzing blood samples from larger cohorts stratified by disease activity, and investigating how viruses persist in the blood despite the innate immune system.

This story was translated from Medscape’s French edition.