Invest in ME Foundation Project Status

UK GUT MICROBIOTA RESEARCH

 

A Role for a Leaky Gut and the Intestinal Microbiota in the Pathophysiology of Myalgic Encephalomyelitis

 

Introduction

From 2007 the charity has focused on a policy of campaigning for better education and for high-quality biomedical research into ME. To this end the charity has begun funding leading edge biomedical research into ME. The UK Gut Microbiota project aims to find whether there is evidence of a leaky gut in ME patients. This is the foundation research project in our proposal for a research and development facility which could lead to a UK Centre of Excellence for ME [1]. 

 

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Latest News

 

August 2014

 

Totals Update £4000 - Target £100,000

 

 

March 2014

 

UEA and IFR Press Releases

IFR Press Release - Click here

UEA Press Release - Click Here

 

February 2014

 

We are now funding future phases of this work to build a solid base of research into ME.

This is open to all academic institutions.

See the Invest in ME Research Grants Policy - click here

Please help us.

The new fundraising thermometer on the right shows our progress in raising funds for the follow-on work.

There is a Donate button at the bottom of this page to help us achieve the new target of £100,000. This will fund a follow-on studentship which will complement the work already underway as we broaden the scope of the study and establish the foundations for a centre of excellence for ME.

 

 

Our Fundraising campaigns

Phase I - Target Reached

Phase II - Target £100,000
   

Phase I - Foundation Project

 

 

 

Project Description

From 2007 the charity focused on a policy of campaigning for better education and for high-quality biomedical research into ME. Having had a generation of poor and under-funded research into ME, a lack of treatments, lack of proper examinations, and a failing of any change to occur or even be contemplated, it became clear that we needed to break the mould. This led to our proposal for a research and development facility which could lead to a UK Centre of Excellence for ME [1]. 

As part of this Invest in ME representatives first met the then Dean of Medicine at UEA, Professor Sam Leinster, in April 2010. This meeting was made possible with the help of our advisor Dr Ian Gibson, former Dean of the School of  Biological Sciences at UEA.

Professor Leinster was willing to help us get started with research into ME and introduced us to Professor Tom Wileman, Director of the Biomedical Research Centre. Professor Wileman suggested developing unbiased research using the genome sequencing facility at the Norwich Research Park, TGAC, to look at all known and unknown viruses in the faecal samples of ME patients. He introduced Professor Carding, a gut immunologist at the Institute of Food Research (IFR), to the project as the emerging science was increasingly showing that the gut microbiota played a major role in many chronic diseases.

Invest in ME funded Professor Wileman's attendance at the 2010 Australian symposium organised by the Alison Hunter Memorial Foundation and the Bond University [2] to get a feeling of the ME research landscape. He and Professor Carding have since chaired, co-chaired/attended all of the research meetings organised by Invest in ME [3].

Professor Carding gave an excellent presentation about the gut in health and disease in 2011 at IIMEC6 [4] and outlined the Invest in ME project to the attendees of the 2013 research meeting [5].

Meanwhile the charity's discussions with Norfolk Primary Care Trust (PCT) had produced an agreement to fund a consultant for the patient examinations. Unfortunately, since the NHS reforms and PCTs having been disbanded our original plans needed to be modified. As there is no consultant at the Norfolk ME/CFS service we asked Dr Bansal from St Helier and Epsom Hospital Trust in Sutton to become involved in the project to identify suitable patients from his patient database. Now we had all the main people in place and set out a funding target of £100 000 to be able to fund a PhD studentship.

Patient volunteers set up the Let’s do it for ME campaign [6] to help us achieve this formidable target within the ME community. It took two years to raise the necessary funds but finally in May 2013 at IIMEC8 [7] we were able to announce that the funds had been raised to begin the PhD studentship at UEA/IFR. The PhD studentship began under the guidance of Professors Carding and Wileman in October.

In addition to this we are pleased to announce that a medical student has also been identified to intercalate and perform a Masters degree within this project with the help of sponsorship from Invest in ME. The charity’s aim is to be able to fund several of these medical students to encourage them to intercalate in ME related post graduate research and thereby improve the knowledge of ME within the healthcare services and within the  medical student environment.

Our aim is to improve education, initiate high-quality biomedical research into ME and raise awareness.

The foundation project is titled “A role for a leaky gut and the intestinal microbiota in the pathophysiology of myalgic encephalomyelitis” [8].

 

 

FAQs on the IiME/UEA Gut Microbiota Project 

The links below open provide more information when you click on them.

Why is this project important?

More research and data is associating ME as an autoimmune disease and research meetings organised by Invest in ME (such as the Clinical Autoimmune Working Group  and BRMEC3 meetings in London) are discussing this.
The majority of the immune system can be found in the gut and it is therefore highly desirable to study the gut microbiota in ME patients. The gastrointestinal tract contains a microbiota consisting of a vast number of bacteria and viruses.
The microbiota are the normal resident bacteria in the gut. There is an increase from top to bottom of the gut, with most being in the lower bowel. There are 10 times as many bacteria than cells in our bodies and bacterial genes are 100-fold. 

The microbiota can influence intestinal barrier function and host defence against microbial challenge. Changes in the microbiota can cause local and systemic chronic inflammation.Genomics provides more accurate identification of bacteria, sequence information transmits to the function of the bacteria, and diet shapes the gut communities.
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. 

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.

This project will be looking for all viruses and determining the relevance of those found.
Furthermore, such a project being performed in the UK will help raise the profile of ME in the UK and Europe as a disease demanding biomedical research.


Where will the project take place?

The project is being performed at the Unversity of East Anglia, and in conjunction with two other major organisations in the Norwich Research Park - the Institute of Food Research and the TGAC.
The studentship will be based in the Norwich Medical School and the Institute for Food Research at Norwich Research Park. 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.


Who are the researchers?

Professor Tom Wileman is Director of the Biomedical Research Centre. Professor Carding is a gut immunologist at the Institute of Food Research (IFR). Both Professors Wileman and Carding have attended our last two Biomedical Research into ME Collaborative meetings. Professor Wileman chaired our "Corridor Conference" round table discussion in 2011 in London and Professor Carding gave an excellent presentation about the gut in health and disease in 2011 at the IIMEC6 2011 conference - available on our 2011 conference DVD.


Why is UEA/IFR the best place to perform the project?

UEA and IFR are world-renowned organisations with some of the best researchers and facilities in the UK.
The institutions and researchers have expertise in this area and are well placed to perform this research.


Is this research new?

Yes, it is and it is using advanced techniques.
Invest in ME originally proposed this in April 2010. It took two years for our supporters - patients and carers and friends
- to raise the required funds to begin this project. Now, in 2013, this area is very topical regarding the study of ME as we move into looking at ME as an autoimmune disease and other establishments are  thinking of performing similar work.


Can this study help move research forward?

Yes, it can and it will.

“I think that this is extremely important because the microbiome in our intestinal tract has the potential to polarize and modulate immune responses. It is imperative, then, that we characterize those."
"That’s one more thing that I want to mention with respect to the microbiome. I think that the microbiome is going to be where the action is."

- Professor Ian Lipkin, John Snow Professor of Epidemiology Director, Center for Infection and Immunity Professor of Neurology and Pathology, Mailman School of Public Health and College of Physicians and Surgeons, Columbia University


How far ahead is the project?

The project began in October 2013. This is a three year studentship project.


When are the first results of this study likely to emerge?

This will depend on how long it takes to recruit sufficient numbers of patients and to fully optimise and validate the assays to be used on the patient samples. The team would, however, expect to have some preliminary findings with 18 months of beginning to receive patients’ samples.


How would leaky gut be investigated as opposed to the microbiome/microbiota metabolism?

There are standard clinical tests that have been used for decades to determine the permeability of the gut wall. It involves the patient drinking a sugar-based solution and then producing a urine sample at a later time point to determine whether or not the consumed sugar has crossed the gut wall and is present systemically and in the urine: a positive finding would be indicative of a leaky gut wall and would warrant further corroborative investigation. A leaky gut would no longer be an effective barrier to intestinal microbes or the factors and antigens they produce which could then gain access to the bloodstream and other parts of the body to trigger inflammation and if uncontrolled, tissue injury.


Does the study involve looking at inflammatory markers?

From a therapeutic standpoint and needing to know more about disease causality there is limited value in looking at or screening samples for the presence of inflammatory mediators or markers in isolation if the possible causes and origins are not known or investigated. Our project will be testing the hypothesis that the originating source of inflammation in ME is the gut and the leakage of microbial products from the gut lumen across and through a compromised gut barrier, which then initiate and perpetuate inflammatory reactions throughout the body. If a "leaky gut" can be established in these patients and we can demonstrate that their immune system and blood lymphocytes have reacted to the presence of microbial products normally found in the gut, then this provides a means of formally identifying over-stimulated immune cells and lymphocytes as a cause of disease and the source of inflammatory mediators, and what their identity and mechanism of action is. This information is of great value in designing more targeted and specific interventional therapies for ME.


How would leaky gut be investigated as opposed to the microbiome/microbiota metabolism?

There are standard clinical tests that have been used for decades to determine the permeability of the gut wall. It involves the patient drinking a sugar-based solution and then producing a urine sample at a later time point to determine whether or not the consumed sugar has crossed the gut wall and is present systemically and in the urine: a positive finding would be indicative of a leaky gut wall and would warrant further corroborative investigation. A leaky gut would no longer be an effective barrier to intestinal microbes or the factors and antigens they produce which could then gain access to the bloodstream and other parts of the body to trigger inflammation and if uncontrolled, tissue injury.


What is the focus of this research?

The study is focused on the cause and consequences of altered populations of gut microbes in ME patients.


Is the study safe?

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.


How can I take part in the project?

For the foundation project patients will be selected from Dr Bansal's patient cohort. This will use standard NHS guidelines and procedures for patient participation.


Will the researchers ask for government funding?

The charity is funding this study in full - thanks to our supporters. Depending on the study results this is an option which will be considered by the the charity and advisors as the project continues.


Who else is advising on the project?

The UEA team are collaborating with Dr Amolak Bansal, who is the consultant immunologist and founder of the CFS service at St Helier Hospital. Dr Ian Gibson has also been the charity's advisor throughout the proposal for an examination and research facility in Norwich Research Park.


What else is Invest in ME doing regarding research?

Invest in ME have run an international biomedical research conference on ME every year since 2006, now attended by representatives from most of the world’s main biomedical ME research teams. We have also initiated, with the Alison Hunter Memorial Foundation of Australia, a biomedical research collaborative meeting to foster collaboration among researchers, including a 2012 meeting on autoimmunity. Autoimmunity is, of course, an important aspect of the possible mechanism of rituximab in ME.
The funds for this project have been raised by supporters of Invest in ME. Via determination and effort and the positivity of the Let's Do It For ME campaign we have been able to raise this funding when nobody else was considering this line of research. As part of a proposal for an examination and research facility which would lead to a Centre of Excellence for ME this foundation project proves what determination can achieve.

Other projects being funded include the UK rituximab clinical trial for ME - a project between IiME and University College London.

Invest in ME are working with researchers, as part of the examinations facility proposal and to support the rituximab trial, on a more comprehensive and detailed analysis of antibodies binding the hypothalamus.

We will also be funding a medical student to perform a Masters degree within the ME gut microbiota project.

More details via this link.

We welcome support from other organisations, companies, groups and individuals for our proposal and we continue to raise funds for other biomedical research projects for ME via our Biomedical Research Fund which will be solely used for high-quality biomedical research.


How can I help?

We welcome your support in the form of donating, fundraising, spreading word of the project and other research being proposed and initiated by IiME, or simply letting us know that you are behind us in this effort. Invest in ME is run entirely by volunteers. There are no salaries and no funds will be used for administration costs. All funds raised will be used in full for financing the biomedical research projects which are initiated. We need to raise awareness and interest from as many sources as possible.


What is Let’s Do It for ME?

Let’s Do It for ME is our fundraising and awareness campaign for biomedical research into ME, led by our supporters. It has its own website, Facebook page and blog and is playing a major part in raising funds for Invest in ME's biomedical research projects. Use these links to learn more -

LDIFME website
LDIFME facebook
LDIFME blog


Can I ask questions about the project?

We will update this page and other pages on the web site with information about the project at regular intervals but if you have something you want to know but don't find it here then please email us at info@investinme.org. We will also accept questions using an interface on this site which will be developed - info@investinme.org

 

 

References:

 

Further Reading

University of East Anglia http://www.foh.uea.ac.uk
Institute of Food Research http://www.ifr.ac.uk
Norwich Research Park http://www.nrp.org.uk/cms.php?pageid=1
Norfolk and Norwich University Hospital http://www.nnuh.nhs.uk
TGAC - The Genome Analysis Centre http://www.tgac.bbsrc.ac.uk
EDP News Story Click here
MP Executive Summary August 2014
FAQ September 2011
BRMEC3 Meeting click here
BRMEC4 Meeting Report click here
   

 

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Our gut microbiome project poster

 

Support ME Awareness - Invest in ME - Invest in ME Research

 

 

 

December 2013



Last Update:    August, 2014