Virus Infection, Reactivation, and the Gastrointestinal Microbiota in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)
The gut microbiome—the community of bacteria and viruses in the intestines—plays a key role in the development of the immune system and in protection against viral infections. At the same time, certain viruses can disrupt both the immune system and the gut microbiome. However, the relationship between viral activity and the gut microbiome, and the role these factors play in ME/CFS, remain poorly understood.
This project investigates the interaction between viral infections and the gut microbiome in ME/CFS patients. The findings may support the development of new diagnostic biomarkers and help identify patients who could benefit from antiviral or microbiome-targeted therapies, such as faecal microbiota transplantation (FMT). In FMT, stool containing beneficial bacteria from a healthy donor is transferred to a patient’s gut to restore microbial balance.
Objective
The aim of this project is to:
- Determine the activity of viruses such as B19, EBV, HCMV, HHV-6, HHV-7, and endogenous retroviruses (remnants of ancient viral infections integrated into human DNA) in ME/CFS patients and healthy individuals.
- Characterize the composition of the gut microbiome (bacteria and viruses) in stool samples from ME/CFS patients and healthy controls.
- Assess the integrity of the intestinal barrier in both groups.
- Investigate the relationship between the intestinal barrier, the gut microbiome, and viral activity.
- Explore how the gut microbiome of ME/CFS patients affects the intestinal barrier and inflammatory responses in a laboratory model.
Approach / Method
The researchers will first assess viral activity in serum, white blood cells, and saliva using biomaterials from the NMCB cohort. In parallel, they will map the gut microbiome and virome (viruses in the gut) through metagenomic sequencing of stool samples.
Next, intestinal barrier function will be evaluated using specific biomarkers in blood and stool. The findings will be compared with microbiome and virome data from participants in the ME/CFS Lines cohort.
Finally, an in vitro intestinal model will be used, consisting of intestinal and immune cells from healthy donors. These cells will be exposed to microbiome samples from both healthy individuals and ME/CFS patients from the NMCB cohort. The researchers will then measure intestinal barrier integrity and inflammatory responses.
Collaboration Partners
This project is part of the Dutch ME/CFS Consortium and Biobank (NMCB), which collects biological samples and clinical data from ME/CFS patients and healthy individuals. The project also collaborates with the ME/CFS Lines consortium, which builds a complementary biobank in collaboration with the Lifelines population study.
Additionally, there is collaboration with researchers from the RESTORE-ME study at the Quadram Institute (Norwich, UK), which investigates whether FMT is a safe and effective treatment for ME/CFS patients.
Patient representatives from the Me/cvs Vereniging and ME/CVS Nederland are closely involved in the project’s design and implementation, ensuring that the research reflects patient perspectives and priorities.
Expected Results
This research aims to provide deeper insight into the relationship between viral activity, the gut microbiome and virome, and intestinal barrier function in ME/CFS. It will also clarify how the ME/CFS microbiome influences inflammation and gut permeability.
The researchers expect to find a link between abnormalities in the gut microbiome and viral reactivation in ME/CFS patients. They also hypothesize that changes in the microbiome contribute to intestinal barrier dysfunction and inflammation.
Insights from this study are expected to support the identification of new biomarkers for ME/CFS and may open avenues for antiviral and microbiome-targeted treatments, including FMT.