Testing of personalized interventions targeting restoration of the gut microbiome in ME/CFS

The objective of this project is to investigate the composition and function of the gut microbiota in ME/CFS and to test a range of interventions in laboratory models that aim to restore the gut microbiota.

The researchers aim to answer the following key questions:

• What types of laboratory models can be developed to study the gut microbiota of ME/CFS patients outside the body?
• What happens in these models when interventions are applied to restore the gut microbiota?
• Which substances (metabolites) are produced by the gut bacteria of ME/CFS patients, both in laboratory conditions and during treatment?
• How do these metabolites affect the intestinal barrier function in laboratory models?
• How can clinical data be linked with laboratory findings to develop personalised interventions for restoring the gut microbiota in different patient subgroups?

The project begins with a comprehensive analysis of the gut microbiota in ME/CFS patients, combining data and infrastructure from the ME/CFS Lines and NMCB consortia. Existing protocols from the ME/CFS Lines consortium will be used to ensure standardisation.

At the same time, advanced laboratory models are being developed . Stool samples are collected using specialised collection tubes to preserve microbial viability.

Samples will be collected from:

• 100 severely affected ME/CFS patients (via ME/CFS Lines)
• 150 ME/CFS patients with varying disease severity (via NMCB)
• 150 healthy controls

In addition to stool collection, biomedical measurements and questionnaires will provide information to explore the role of the gut microbiota in symptom manifestation among ME/CFS patients.. These samples will form the foundation for developing laboratory models that reflect the in vivo gut microbial composition of ME/CFS patients.

Two complementary intestinal models are being used:

1. The i-screen model
   This model allows researchers to study how gut bacteria grow and respond to specific treatments, such as probiotics and prebiotics, and to identify functional changes in microbial activity.
2. The InTESTine™ model
   This model uses cultured intestinal tissue in a controlled setup to study how bacterial metabolites interact with the intestinal wall and influence barrier integrity and immune responses.

This project is a collaboration between the ME/CFS Lines consortium and the NMCB consortium. The multidisciplinary team includes researchers from: the Netherlands Organisation for Applied Scientific Research (TNO),the University of Groningen, the University Medical Center Groningen (UMCG), experts in occupational health and medicine and international partners at the University of Vienna

Active involvement of ME/CFS experts and patient representatives is an essential part of this project. Representatives from 2 ME/CFS organisations (MECVS Nederland and the ME/cvs Vereniging)) contribute to all stages of the project: preparation, execution, and dissemination. Regular contact with patient representatives ensures that the research remains patient-centred and relevant.

This project will establish innovative laboratory models that accurately represent the gut microbiota composition of ME/CFS patients. These models will be used to test various microbiota-restoring interventions and to measure their effects on: the composition of gut microbial communities, the production of bacterial metabolites, the function of the intestinal barrier.

The findings are expected to reveal which interventions has an effect on the composition of the gut microbiota and which interventions affects the production of substances (microbial metabolites). 

Additionally, the project will provide insights into differences among ME/CFS patients based on their gut microbiota profiles and the laboratory models. This can help develop personalized interventions targeting gut microbiota restoration and guide the direction of more patient-centered clinical (follow-up) research.