The Gut Microbiota Research is the first element in Invest in ME Research’s proposal to establish a Centre of Excellence for ME in the UK.

The focus of the research programme is the role of infection and the immune system in the pathophysiology of Myalgic Encephalomyelitis and most of the immune system is located in the gut. This research will be looking for all viruses and determining the relevance of those found.

Thanks to extraordinary efforts and dedication of patients and their carers, families and friends the £100,000 needed to enable this programme of biomedical research to begin was crowdfunded by May 2013.

This funded a PhD studentship project under the guidance of Professors Tom Wileman and Simon Carding (pictured in tweet with Daniel Vipond and Let’s Do It for ME Bear) based at Norwich Research Park, involving Norwich Medical School, Quadram Institute Bioscience, University of East Anglia, and Earlham Institute’s sequencing facilities.

These are world-renowned organisations, institutes and researchers, with expertise in this area and well placed to perform this research.

The foundation study titled ‘A role for a leaky gut and the intestinal microbiota in the pathophysiology of myalgic encephalomyelitis’ aims to determine if alterations in intestinal barrier function and/or microbiota exist in ME patients, and whether microbe-driven inflammatory responses can provide an explanation for the pathophysiology of ME. It is described below along with subsequent studies in the programme.

Importantly this foundation research project will also enable a database to be established for use in further research. It was first proposed in 2010 by the Invest in ME Steering Group formed to instigate the setting up of the examination and research facility. More on the proposal here.

 

GUT MICROBIOTA and B-CELL STUDIES

We helped raise a further £700,000 for next phases of the Invest in ME Research Centre of Excellence biomedical research programme and to help build a solid base of research into ME, funding follow-on studentships at UEA and UCL which complement the work already underway to establish the foundations for a Centre of Excellence for ME.

Further 3 year studentships at UEA/IFR under the supervision of Professors Carding and Wileman are joint funded by the Faculty of Medicine and Health Sciences and Invest in ME Research.

The multidisciplinary projects benefit from the collaborations Invest in ME Research have built up over the years since 2006 of organising and hosting international biomedical research conferences and researcher meetings.

In particular they benefit from current collaborations with the neuroimmunology group of Professor Angela Vincent at Oxford University; Professor Jo Cambridge’s group at University College London, leading research in B-cell depletion for autoimmune disease and including a PhD studentship funded by Invest in ME Research; and Professor Maureen Hanson’s group at Cornell University, USA, where one of the medical students involved in the Invest in ME Research Centre of Excellence research spent three months. More about the Medical Students scheme here.

Summary of each of the PhD studentship projects below. For full details click here.

A role for a leaky gut and the intestinal microbiota in the pathophysiology of myalgic encephalomyelitis

Recent studies [Fluge et al (2011) Plos ONE 6:e26358] point to a link between autoimmunity and myalgic encephalomyelitis (ME or ME/CFS).

Autoimmune reactions lead to inflammation, increased permeability of blood vessels and migration of lymphocytes to sites of injury. Microglia within the brain can be primed during chronic inflammatory diseases, but can then induce inflammation in the brain when they are triggered by a second inflammatory challenge such as a systemic microbial infection. This raises the possibility that the damaging neuro-inflammation seen during ME may be triggered by systemic infections.

The gastrointestinal tract contains a microbiota consisting of a vast number of bacteria and viruses. The microbiota can influence intestinal barrier function and host defence against microbial challenge. Changes in the microbiota can cause local and systemic chronic inflammation. This project will determine if alterations in intestinal barrier function and/or microbiota exist in ME patients, and whether microbe-driven inflammatory responses can provide an explanation for the pathophysiology of ME.

  • The project began in October 2013.

  • The cohort selected fit the Canadian Consensus Criteria and include the severely affected.

  • The studentship is based in the Norwich Medical School and Quadram Insitute Bioscience.

  • The student will analyse serum samples from patients with ME for integrity of intestinal barrier function.

  • Faecal samples from patients will be analysed by high throughput pyrosequencing and appropriate bioinformatics to profile the microbiota in terms of bacteria and virus populations.

  • Parallel studies will assess microbiota metabolism by LC/MS/NMR analysis by the IFR Metabolomics Partnership.

    For full details click here

 

 

Defining autoimmune aspects of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

The aim of this PhD project is to test the hypothesis that ME is an autoimmune disorder originating in the gut as a consequence of altered intestinal permeability (leaky gut) leading to exposure of the immune system to commensal gut microbes and their products and the generation of pathogenic (auto) antibodies cross-reactive with antigens expressed in the central nervous system (CNS).

For full details click here

 

 

Gut Viruses and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

This PhD project will investigate whether the underlying causes of ME are related to the presence of specific virus populations within the gut virobiota. Using high throughput DNA/RNA sequencing technology and bioinformatics tools we will determine if and how both resident gut bacteria and virus populations changes with disease progression and if a distinct virobiota signature can be identified in ME patients.

For full details click here

 

 

Investigating alterations in the intestinal virome in ME

This PhD project will investigate and aim to answer important questions concerning the role of the enteric phage/virome in ME. Specifically, can long-read sequencing identify new enteric phages, many of which may have been locked within the ‘viral dark matter’? Do the phages populations differ between patients and controls? Can the phages identified reduce populations of ‘beneficial bacteria’ and/or affect the metabolism of the microbiota? Can phage DNA profiling be used in biomarker development for ME?

For full details click here

 

 

Extended B cell phenotype in patients with myalgic encephalomyelitis/chronic fatigue syndrome: a cross‐sectional study

A preliminary B-cell study was designed to confirm and extend the earlier work of Dr. Amolak Bansal [1] on B-cells but using a different cohort of ME patients. This was advised as prerequisite to a UK trial of rituximab but also a useful study in its own right. The study was published in the official Journal of the British Society of Immunology, Clinical and Experimental Immunology.

For full details click here.

 

 

The potential role of B cells and their products in ME/CFS Patients

Recent studies have identified abnormalities in the blood of patients, which have strengthened the suspicion that the immune system contributes to ME/CFS. Changes in populations of white blood cells, called B cells, in ME/CFS have been reported by several research groups including those in the UK. In addition, treatment with anti-B cell therapy using Rituximab by Fluge and colleagues in Norway have shown benefit to ME patients. This PhD project will investigate whether certain B cell products (antibodies and soluble factors) are involved in ME/CFS.

For full details click here.

 

 

Frequently Asked Questions
 

For more information & updates on the projects visit

www.investinme.org

 

Invest in ME Research – Let’s Do It!


 

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