Blog: Is a disrupted immune response to bacteria and viruses a factor in ME/CFS?

The gut microbiome consists of trillions of bacteria, viruses, yeasts and fungi. Together, they play a crucial role in the functioning of the immune system. When the immune system is disrupted, it reacts to the gut microbiome. These immune responses can lead to inflammation in the intestines and the extreme fatigue and symptoms of post-exertional malaise (PEM) that people with ME/CFS often experience.
‘In our previous study we compared 40 ME/CFS patients with the same number of similar but healthy people’, says Vogl. ‘During that study we discovered that the ME/CFS patients had different antibodies from the healthy individuals. These were antibodies against certain bacteria in the intestines. We want to examine this further, because a difference in antibodies might explain how ME/CFS develops. 
‘We saw, for example, that people with severe ME/CFS have certain antibodies against healthy gut bacteria. Their immune system responded to healthy gut bacteria more than twice as often as that of healthy subjects. This might mean that the immune system of ME/CFS patients sees these healthy bacteria as “dangerous”. We want to explore if this is actually the case’, Vogl explains. 

‘We are using the Lifelines cohort to collect patient data. Lifelines has been collecting data and blood samples from 167,000 people every five years for the last 15 years. Some of the participants have developed ME/CFS during this time, so we have their biomaterial from before and after their diagnosis. This is very useful for studying differences in the immune system, to find out what might have caused the disease. We are using data and biomaterials from 800 healthy individuals and 800 individuals with ME/CFS from the Lifelines cohort.
‘Besides the materials and data from Lifelines, we also need faeces samples from patients and healthy individuals to gather information about the gut microbiome. Stool samples are currently being collected from ME/CFS patients as part of a parallel project in the ME/CFS research programme. We will also include samples from 100 people with severe ME/CFS, in collaboration with the Dutch ME/CFS Cohort and Biobank (NMCB)', says Zhernakova.

Vogl explains the techniques they are using: ‘If we want to know how the immune system responds to the gut microbiome, we have to identify lots of immune responses. So we are using a special aid in our study: a library of protein fragments from known bacteria and viruses. We can use the library to identify which antibodies are present in the blood of patients with ME/CFS and in healthy people, and what bacteria and viruses they target.’

‘We are also using an innovative technique: machine learning. This will allow us to compile information on antibody responses to thousands of bacteria and viruses. It’s not possible to analyse such enormous quantities of data with other research techniques’, Vogl explains. 
'We’ve never looked at the immune system, gut microbiome and common infections in ME/CFS on such a large scale before. Machine learning works with algorithms. An algorithm tells the computer what to do, and it allows us to train the computer to find regular combinations of bacterial and viral structures that bind to antibodies. If we repeat this many times, we can identify patterns in these combinations and see whether there are differences in the immune response and antibodies of healthy individuals and patients.' 

‘At the moment, reported symptoms and questionnaires are used to diagnose someone with ME/CFS’, says Zhernakova. ‘This happens after symptoms have already occurred. Our study will give us a better understanding of the cause of the disease, and that should help in determining the best treatment, or in making a diagnosis. It might then be possible to make the diagnosis before a patient gets symptoms, so our work will hopefully help with early treatment of the disease, and maybe even the prevention of ME/CFS through vaccination.'