Viral blood signature discovered for Crohn’s disease

Crohn’s disease is a chronic inflammatory disease of the intestine affecting 0.4% of the European population. Its causes are multifactorial, including both genetic and environmental components, with a key role played by the gut microbiota. The strong association between this condition and changes in the bacterial fraction of the microbiome has led scientists to look more closely at the bacteriophages found in the gut in search of a viral signature for the disease. However, the task of analysing the collective viral genetic content – the virome – in the gut proved too complex. So great is this virome’s diversity, in fact, that no two individuals share the same species profile, making it impossible to compare the viral communities involved.

In search of an alternative source of viral information, scientists from INRAE, Sorbonne University and the Paris public hospitals (AP-HP Saint Antoine) turned their attention to the blood virome. The possibility of this virome’s existence has only recently emerged, as blood was long thought to be sterile, but the high permeability of the intestinal barrier induced by Crohn’s disease led the team to suspect that the viral composition of the blood could be affected, making this compartment a candidate for investigation.

Confirmed blood virome in all humans

The research team compared the blood samples of 15 patients with Crohn’s disease with a healthy control group of 14 subjects. Their first major finding was that a blood virome does indeed exist, even in healthy subjects. Low concentrations of viral particles were present in the blood of both groups (around 100,000 particles per mL of blood, compared with an estimated billion particles per gram of faeces in the gut virome). Bacteriophages formed the greater part of both groups, with an average of 150 species in each individual, with just a small minority of human viruses (non-pathogenic Anelloviruses) present.

The second important discovery was that there was a distinct difference between the types of bacteriophages found in the blood samples from the healthy control group and those from the group of Crohn’s disease sufferers. Whereas a certain number of bacteriophages known to target bacteria from the genus Acinetobacter[1] were observed in the samples from the control group, these bacteriophages were almost absent from the blood samples of individuals with the disease. And, by contrast, a wide variety of bacteriophages that target typical hosts, including intestinal bacteria, were found only in the blood of subjects with the disease. This could be linked to the translocation of some viruses from the intestinal microbiome to the blood due to the reduced gut barrier function caused by the disease.

These results both prove the presence of a blood virome in all individuals and enable a signature for Crohn’s disease to be detected.

They open up new research directions that might include the study of the translocation of bacteriophages due to gut barrier dysfunction, further blood sample analysis (employing a larger validation cohort to consolidate results, or investigating more homogenous groups with matching disease states), or the investigation of the presence and role of viruses in the blood despite an operational immune system.