The Gut Microbiota Research Project is the first element in Invest in ME Research’s proposal to establish a Centre of Excellence for ME in the UK.
The first part of this project titled ‘A role for a leaky gut and the intestinal microbiota in the pathophysiology of myalgic encephalomyelitis’ aims to find whether there is evidence of a leaky gut in ME patients. It 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.
Thanks to extraordinary efforts, dedication and sheer hard work by patients and their carers, families and friends the £100,000 needed for this research was successfully crowdfunded in May 2013. (New target £200,000).
The project is a three year studentship project under the guidance of Professors Simon Carding (pictured) and Tom Wileman. It began in October 2013 and is being performed at the University of East Anglia, and in conjunction with two other major organisations in the Norwich Research Park – the Institute of Food Research and the The Genome Analysis Centre’s sequencing facility. The studentship is based in the Norwich Medical School and the Institute for Food Research at Norwich Research Park.
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.
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.
‘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. This is a three year studentship project.
The cohort selected will fit the Canadian Consensus Criteria and include the severely affected.
The studentship will be based in the Norwich Medical School and the Institute for Food Research at Norwich Research Park.
The student, Daniel Vipond (pictured above front), 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.
We are now fundraising a further £100,000 for future phases of this work and to build a solid base of research into ME. This will fund follow-on studentships 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.
Project II involves two further 3 year studentships at UEA/IFR under the supervision of Professors Carding and Wileman 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 10 years 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 clinical trials of B-cell depletion for autoimmune disease; and Professor Maureen Hanson’s group at Cornell University, USA.
Summary of each of the studentship projects below. Full details of the Gut Microbiota Projects are on the Invest in ME Research website 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).
‘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.
Professor Simon Carding, Leader of the Gut Health and Food Safety Research Programme, Institute of Food Research and Norwich Medical School at the University of East Anglia, was interviewed by BBC journalist Susie Fowler-Watt for BBC Look East and describes the project which Invest in ME is funding (on youtube here).
The PhD and intercalating medical students involved in the IIME-funded UK gut microbiota research participated in a panel session at the 10th International ME Conference (IIMEC10) in London on 29th May. Bharat Harbham, Daniel Vipond and Navena Navaenanarathrama answered questions from the audience about their research and their impressions of ME, along with Fane Mensah, PhD student at the IIME-funded B-cell/rituximab study at UCL. The students gave insightful and interesting responses and provided a view of the next generation of researchers into ME.
Professor Tom Wileman presented preliminary results of the UK gut microbiota research in London in June at the 11th Invest in ME Conference (IIMEC11) and 6th Biomedical Researchers into ME Colloquium (BRMEC6). Click here for IIMEC11 Conference Report and IIMEC11 DVD with full presentations by all the speakers.
“The next steps in the Carding lab are to correlate phage populations
in patients with severe disease compared to house-matched controls.
This work has the potential to elucidate more distinct subpopulations
within current ME/CFS classifications and of upmost importance,
has the potential to influence therapeutics, providing much-needed
approaches in preventing and managing a disease in need of confronting.”
“If the detailed research efforts can be accelerated and conducted in a co-ordinated fashion,
it will support the development of therapeutics to address and alleviate the diverse range
of incapacitating symptoms of ME/CFS, and will then ultimately provide much hope in moving
towards prevention of a disease ignored for too long.”
SEPTEMBER 2016 UPDATES
Two new PhD students will start in September/October in Norwich Research Park.
One is funded by Invest in ME. The other is a self-funding student who is experienced in laboratory work
and was specifically interested in participating in the ME research which has been started at UEA/IFR.
A third student position funded by Invest in ME is being advertised. With Daniel Vipond,
this makes four PhD positions current or planned involved with the research into ME at Norwich Research Park.
The charity is also aiming to keep the MedRes studentships going as these have turned out to be very successful in many ways. These highly motivated medical students are not only very helpful for the research projects but they also become better ME-educated doctors as well as influencing their student peers. Some even stay involved in ME research!