Columbia University – Center for Infection and Immunity has seriously upped the ante on the initial microbe discovery project in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Their rigorous new study could point the way to diagnostic tests, and even treatments – but first they need the funds to complete the work.
The current project at the CII at Columbia University in New York is called ‘Microbial Discovery and Immunity in ME/CFS’. The team has published research showing the immune system of patients who have recently developed ME/CFS look markedly different from those who have been ill for much longer. That immune signature work was partially supported by the Chronic Fatigue Initiative, who have also funded CII studies into pathogen discovery, metabolomics, proteomics, epigenetic analysis and immune profiling. There has been a wealth of investigation in process at CII – not to mention their other collaborative work in progress.
Comprehensive deep diving
The study intends to test the hypothesis that ME/CFS cases and controls have different bacterial, fungal or viral microflora in the oropharynx (mouth and throat regions), lower gastrointestinal tract (gut) and blood in a massive, well-powered study.
This will be the first ME/CFS study to look at the microbiome over time. They are collecting stool and saliva at four different times over the course of a year, allowing the researchers to see if the changes in microbiome and immune system are related to changes in symptoms over time. Blood is also collected at the first and last time points.
All ME/CFS cases have been carefully diagnosed and meet both Fukuda criteria and the stricter Canadian criteria. The study will have 125 ME/CFS patients and 125 healthy matched controls.
[pullquote align=”left” cite=”” link=”” color=”” class=”” size=””]The CII only have the funding to rigorously collect, organize and store samples. They have NO funding to test and analyze the samples – which will generate a colossal amount of data from a large and carefully diagnosed, representative group of patients. If they get the funding they intend to do any or all of the following testing and analysis.[/pullquote]
First off, the CII plans to investigate the human microbiome as it relates to ME/CFS, to determine how bacteria, fungi, viruses – and the immune response to them – contribute to the disease.
They will use high-tech methods to identify and quantify all the different bacteria (bacteriome), fungi (mycobiome) and viruses (virome) in each person’s gut and mouth/throat microbiome, effectively creating a map of each person’s microbiome. This alone is a huge undertaking in order to identify potential triggers of immune response and or metabolic problems.
The team then intends to apply a series of even more new technologies to test the blood for proteins, metabolites and immune markers to tease out what’s going wrong in people with ME/CFS.
VirCapSeq-VERT is the Virome-Capture-Sequencing platform for Vertebrate viruses. This is powerful new technology invented by CII and hailed by Scientific American as one of the “world changing ideas” of 2015. It is a system to broadly screen for all viral infections in vertebrates, including humans. This test increases viral matches from 100 to 10,000-fold compared with conventional high-throughput tests.
This testing identifies any virus that has ever been found to be in a person – 1.7 million agents are reported to be tapped through this testing. This work would clearly increase the yield of viruses detected in people with ME/CFS.
Proteomics, is the large-scale study of proteins in the blood, which gives researchers a protein ‘signature ’. By looking at all the proteins in the blood, rather than just focusing on a few, researchers get a much fuller picture of what’s going on, or wrong, in the body.
The aim is to identify biomarkers in blood that can be used for diagnosis, to predict illness progression and track responses to interventions. Biomarkers may also help identify targets for new therapies.
Metabolomics, in a similar way to proteomics, is the study of ‘metabolites’, all the small chemicals in any tissue or the blood such as amino acids or hormones that result from metabolic processes in cells. This yields clues about what’s gone wrong in the body. Increasingly researchers are turning to the new field of metabolomics to understand disease. Ron Davis recently reported fascinating preliminary metabolomics findings in ME/CFS that suggest something is going seriously wrong with how patients produce energy from food.
As with proteomics, metabolomics may be used to identify potential ‘biomarkers’ that can be used for diagnosis and therapeutic targets. For instance, if the work identifies specific problems in energy metabolism, researchers can aim to tackle these problems with drugs, or even with supplements.
To identify biomarkers for diagnosis, prognosis, as well as potential therapeutic targets, and to determine the history of exposure to infectious agents that may trigger onset or exacerbation of ME/CFS.
The team will look to see if particular versions of genes are associated with subgroups that may predict course of illness or response to different treatments.
Epigenetics is the main system that turns some genes on and some genes off long-term, without affecting the DNA sequence itself. This study will look for epigenetic signatures that may be associated with ME/CFS and that may correlate with infectious or other triggers.
Homing in on ME/CFS
This study represents a comprehensive, robust investigation of the priority areas of research for ME/CFS that Dr. Lipkin recently identified in his letter to the NIH. This work now includes complex data mining and more. This can only be described as a tour de force that will home in on molecular detail – dive deeper, solidify findings and parse out subgroups. This is just the type of study that will help lead to diagnostic tools and possible treatment therapies. Dr. Lipkin also explained in the letter to the NIH that their aim is to develop a Clinical Trials Unit to:
[pullquote align=”full” cite=”” link=”” color=”” class=”” size=””]“rigorously examine interventions, including probiotic/nutritional, biological (e.g., immune regulators; anti-cytokine antibodies), medication and potentially, microbiome-related (e.g., fecal microbiome transplantation, other) approaches.”[/pullquote]
As the team already has close links with five expert clinics, the trials unit is well placed to recruit patients to get trials moving as fast as possible. This study would be part of the building block foundation for the establishment of a center of excellence in ME/CFS research, that will hopefully ultimately have a global component.
These researchers need the community’s support with thousands of donations and shares about the study. It isn’t about the amount of dollars people donate, but about how many we can get to support, share and donate something: every little bit counts!
You can donate directly to this study through CII’s secure site:[button_color url=”https://giving.columbia.edu/giveonline/?schoolstyle=5881&alloc=21677″ content=”Donate to this project!” target=”https://giving.columbia.edu/giveonline/?schoolstyle=5881&alloc=21677″]
Thank you so much for your support!
Want more information? Read the full article about the study on the Microbe Discovery Project Website.