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Lipkin's Monster ME/CFS Study: Microbes, Immunity & Big Data

Discussion in 'Phoenix Rising Articles' started by Simon, Aug 22, 2016.

  1. Simon


    Monmouth, UK
    Simon submitted a new blog post (BUT IS NOT THE AUTHOR):

    The Microbe Discovery Project outlines an ambitious new study by top researchers that has collected patient samples, but needs desperately funds to complete the work.

    Dr. Ian Lipkin

    Columbia University's Center for Infection and Immunity(CII) has seriously upped the ante on the initial microbe discovery project in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Their impressive, rigorous new study could point the way to diagnostic tests, and even treatments – but first they need the funds to complete the work.

    ME/CFS is an urgent challenge in clinical medicine and public health. There is no diagnostic test or specific treatment for ME/CFS, and in the United States alone there are a minimum of 836,000 afflicted individuals. Social and other costs for patients and their families are phenomenal, with medical care costing $24 billion - just in the US. While the US domestic cost is high, ME/CFS is very much a global problem.

    The current project at the CII at Columbia University in New York is called ‘Microbial Discovery and Immunity in ME/CFS’. It builds on the foundation they established during the National Institutes of Health’s (NIH) multicenter study of XMRV/pMLV viruses in ME/CFS, led by Dr. Lipkin.

    Since that first study the team has published very significant 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.

    Dr. Mady Hornig

    The CII has pioneered many relevant research techniques, has a stellar track record in research as well as unique expertise. The laboratory team has extensive experience in infectious disease epidemiology, microbe discovery and de-discovery, as well as in the development of sensitive blood tests and animal models needed to test for causal relationships and investigate disease causing mechanisms. Pathogens are not the only string in CII’s bow, their work also encompasses the immune system and neuro-immune areas.

    It is hard to exaggerate how much rigor and expertise CII brings to the field of science in ME/CFS. They carefully investigate and go where the leads take them. With all this early investigative work under their belt - this new monster study is suggestive that the CII has good leads they are following. The Microbe Discovery Project team is ecstatic to bring you more details!

    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. By rigorously characterizing cases and controls and using state-of-the-art methods for identifying microbes, even currently-unknown ones, the CII will also study patients and controls for evidence of differences in immune system function and metabolic function.

    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.

    Patients come from five expert centers for ME/CFS research and treatment across the United States. These include Dr. Lucinda Bateman, Bateman Horne Center, Salt Lake City; Dr. Nancy Klimas, Institute for Neuro Immune Medicine, Nova Southeastern University, Miami; Dr. Susan Levine, Private Practice, New York; Dr. Jose Montoya, Infectious Disease Clinic, Stanford and Dr. Daniel Peterson, Sierra Internal Medicine, Incline Village. The team has now recruited all the patients and controls they need, and enrollment is closed.

    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.



    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.

    Pathogen hunt

    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 has much greater sensitivity than the current standard molecular techniques, and 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.


    Visualisations help researchers understand with complex data
    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.

    There is some important key study strengths that are worth noting:

    • The study is a good size, big enough to robustly detect even modest differences between patients and controls, and to tease out subgroups.
    • Each of the four samples taken from every patient is limited to a three-month seasonal time frame to take into account natural, seasonal variations in bacterial, fungal, viral communities and immune system function.
    • Patients come from strategic geographic distribution of sites across the United States.
    • They will also collect data throughout the study on any new diagnoses or medications.
    • A big effort has been undertaken to recruit a diverse population of patients and controls so that they will be more representative of the whole patient population. This means that any conclusions should apply to most patients, rather than being specific to a particular type of patient recruited for a particular study.
    • Clinics will also indicate whether or not patients have cognitive problems (eg. memory or concentration) to help see if this identifies a clear subgroup.

    Dr. Lipkin also explained in the letter to the NIH that their aim is to develop a Clinical Trials Unit to:

    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.

    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.

    The Crunch


    There are no two ways about it – this study needs funding. More than a quarter of samples and questionnaires have already been collected and this analyses needs to get moving. They could be testing and analyzing these right now if the funds were available. The cost is often a lot more for analysis than collection, especially with this type of testing. The CII team is actively seeking funds to complete the work.

    Our patient-led Microbe Discovery Project with all the support from the ME/CFS global community has helped to raise over $1.5 million in funds for CII research - our community made that happen. These funds along with an NIH NINDS grant and heavy subsidization by CII, enabling this collection.

    CII needs at least $5 Million to test and analyze the samples

    So far, the NIH has only given the researchers enough to partly cover recruiting patients and collecting samples, but the study is stranded without the funds for the all-important tests and analysis. We sincerely hope the NIH will decide to help make up some of the shortfall, but can we afford to wait? See our previous blog.

    Too many people are too sick. Too many people have no support, help or treatments. There is a huge and urgent need for high quality research, and the CII team really needs our community’s help - so that they can help patients. We are still in a position of needing to bail-out mainstream research.

    If you have ME/CFS, donating to great research is like an investment in better treatments. Think of the vast collective amount spent by patients on doctor’s appointments, think of all the trial medications and supplements that haven’t worked - ending up in the bin. If we spent the equivalent of one doctor’s visit or the cost of a supplement on investing in research – we can help get this study funded!

    Every donation counts and every share counts! Please help

    Thousands of donations are needed: you can give on CII’s secure site.

    Spreading the word with our blogs on Facebook or other social media helps to gain more donations, and can also lead to large donations. If you would like some more background information, take a look at the the Microbe Discovery Project's resources page. You can also subscribe to our blog, so you won’t miss out on important news.

    Thank you so much for your support!

    This is blog is taken from The Microbe Discovery Project website. A shorter version was published at #MEAction.

    Support Phoenix Rising

    Phoenix Rising is a registered 501 c.(3) non profit. We support ME/CFS and NEID patients through rigorous reporting, reliable information, effective advocacy and the provision of online services which empower patients and help them to cope with their isolation.

    There are many ways you can help Phoenix Rising to continue its work. If you feel able to offer your time and talent, we could really use some more authors, proof-readers, fundraisers, technicians etc. and we'd love to expand our Board of Directors. So, if you think you can help then please contact Mark through the Forum.

    And don't forget: you can always support our efforts at no cost to yourself as you shop online! To find out more, visit Phoenix Rising's Donate page by clicking the button below.


    Continue reading the Original Blog Post
    Last edited: Aug 22, 2016
  2. Cheesus

    Cheesus Senior Member

    Thanks for writing this; it is really excellent. I'm feeling motivated and excited to help raise some funds!!

    One question I want to ask. You state:

    Am I correct in thinking that their hypothesis is that different subgroups have different microbial aetiologies? Have I interpreted that correctly"?
  3. TigerLilea

    TigerLilea Senior Member

    Vancouver, British Columbia
    I took it to mean that people with ME/CFS would have different microbial aetiologies from the controls. I didn't read it as different sub-groups within ME/CFS.
    aimossy and Simon like this.
  4. Simon


    Monmouth, UK
    The post is from the Microbe Discovery Project, I simply submitted this and am not the author. But as I understand it there are a few different possibilities.

    There could be a common mechanism to mecfs, driven by the gut, but with different factors at play in causing the immunological problems, and if that's the case there would be different treatments for bacterial/viral/fungal driven disease. Or it could be just an association (or a result of illness rather than a cause). Or other stuff.... But they hope that by looking over time, and by collecting a lot of immune, metabolomic, proteomic etc data they will have a much better chance of finding what's driving the illness, which may be microbiome problems, or may be other things. Though clearly they suspect the microbiome, hence the study.
    bertiedog, AndyPR, Solstice and 3 others like this.
  5. Cheesus

    Cheesus Senior Member

    Thank you for that clarification.

    And if it wasn't you that wrote it, then I must compliment you on how very artfully you managed to submit it :p:D
    AndyPR, Webdog, aimossy and 1 other person like this.
  6. Forbin

    Forbin Senior Member

    I wonder if some kind of infection/imbalance in the microbiome could in some way chronically stimulate the vagus nerve, leading to some of the autonomic problems seen in ME/CFS. My onset began with a kind of dizziness and a "bottom has dropped out" kind of feeling that I had previously associated with "food poisoning." One doctor suggested this might have been a "vagal episode," but such episodes are acute and transient. Some aspects of ME/CFS, however, almost seem like a chronic, low level version of the vaso-vagal response.

    I know Dr. Michael Van ElZakker at Harvard is interested in a link between ME/CFS and the vagus nerve - although I think he believes it is a direct infection of the nerve itself. I'm more suggesting that vagus nerve might be responding to some kind of chronic disruption of the microbiome as if it was some kind of endless food poisoning/"injury" (perhaps a bad analogy).
    Learner1 likes this.
  7. frog_in_the_fog

    frog_in_the_fog Test Subject

    This is an incredible endeavor that will shed light on what were once the darkest regions of research. I look forward to following this exciting work, and hope that it will be fully funded.
    Forbin, Webdog, aimossy and 1 other person like this.
  8. bel canto

    bel canto Senior Member

    Livewello has reported on at least one snp that is connected with significantly less biodiversity in the gut, and is associated with a number of conditions, including some autoimmune such as crohn's. Being away from home, I can't access my account to locate the information. It will be interesting to see if genetic differences such as that one show up in these studies. It's likely to be at least one piece of the puzzle for some.
  9. aimossy

    aimossy Senior Member

    Last edited: Aug 29, 2016
    AndyPR and Simon like this.
  10. AnnaC


    I'm aware of that Livewello report. My genotype is AG which makes me a secretor or in Livewello's words: "...may have typical microbiome species diversity, due to AG genotype for rs601338 compared to people with other genotypes. Other clinical, genetic or environmental factors may influence this outcome."

    The key to any and all genetic analysis is to keep that last sentence in mind at all times.
    "A study of non-secretor (FUT2 rs601338 AA genotype) and secretor (GG and AG genotypes) adults of western European descent showed that non-secretors had lower species richness than the secretors, and that secretor status and FUT2 polymorphism appear to be key drivers affecting the individual variation of human intestinal microbiota."

    Livewello description:

    FUT2 Gene and the Gut Microbiome

    44% of people with European ancestry carry the A allele for rs601338
    Population genetics:
    The allele version of occurs in 49% of African, 34% of American, 0% of East Asian, 44% of European and 28 % of South Asian. Data obtained from 1000 Genomes Project Phase 1

    Of note:
    0% of East Asian, yet ME/CFS is well studied in Japan
    Last edited by a moderator: Aug 30, 2016
  11. Valentijn

    Valentijn Senior Member

    Not quite. Those numbers are for allele frequency, and people have two alleles. So 69% of Europeans have AG or AA genotypes, 74% of Africans, etc.
    Sushi likes this.
  12. Sing

    Sing Senior Member

    New England
    I get concerned that the researchers are motivated more by a fascination with new technology which works as a status symbol in the field. The companies which make the new technology are also promoting it like made and trying to make money off of it. The new technology is also useful to try to impress government funding sources that the research will be more productive and successful, so it is a good way to get money, prestige and attention. What can be missing though is expert-level understanding of ME/CFS. This understanding does not come quickly to newcomers or without a great deal of study and experience. That is why I think the most important thing in any research project is the advice and guidance it gets from our relatively few expert clinicians in the field. Human understanding is at the top of the chain for impressive "technology". There is absolutely no point to fancy new gadgets and tools in the hands of those who don't know what to apply them to--when, if, where and for what purpose as it relates to the overall understanding. But over and again, the money is roped in for the fads, then there is disappointment when little or nothing emerges as useful and relevant. Then there is a further abandonment of the ME/CFS field as hopeless or all in their heads. So that is why I take a sceptical view of the big noise over new technologies. Our hopes go up and then they go down again in a crash. Get the expert clinicians to guide the research. That is the most efficient way to our goals.
  13. BurnA

    BurnA Senior Member

    I couldn't disagree more.

    We have little to no understanding of this disease despite every patient undergoing countless tests. That's tells me that past and current technology isn't where it needs to be to diagnose this disease.

    We are getting there, but only because of advances in technology.

    Thses aren't new gadgets to play with, they are enabling our expert clinicians and researchers to understand more.
  14. akrasia

    akrasia Senior Member

    I think it's very important from the point of view of accountability not to frame the history of m.e. as leading inevitably to employing the machinery of big data. The proposed Lipkin/Hornig "Monster" study, Naviaux's paper, and Ron Davis's work are all very important and should be supported. These are all actual or potential great steps forward.

    We can argue,however, whether we should confer necessity on these projects. In other words, were there approaches to the disease that could have been investigated decades ago but were undiscovered or unexplored due to stigma and the marginalization of the illness. Was M.E. so elusive that its neglect can be rationalized, that it could only be welcomed into the Valhalla of legitimacy escorted by whiz bang technology? Who knows what the landscape would have looked like if it had been properly funded?

    At the recent Invest in M.E. conference, Davis pointed out that scientists should be encouraged to do what they're good at and if what they're good at entails using this technology, so be it.
    Last edited: Sep 1, 2016
    Soul Creator likes this.
  15. aimossy

    aimossy Senior Member

    I'm not sure why the above link I posted is broken, but here is a link to a large forum thread discussing the study.
  16. Humanrights


    Humm it all boils down to electropollution

    We have different biochemistry.
    Some are transmitters and some are recivers and some are both.

    Like Lyme it links into electropollution.

    Too many positive ions pullin toxins and infection.

    Something I read resently spirochetes cause lead and heavy metals to come out of solution. Link between electromagnetic fields. The infection helps create its own perpetual environment. Lead poisoning and Lyme can have similar symptoms.

    Something similar is happening with ME/CF.
  17. A.B.

    A.B. Senior Member

    100% support for Lipkin here.
    Forbin, lauluce, rosie26 and 3 others like this.
  18. acer2000

    acer2000 Senior Member

    Any update in the study?
    lauluce likes this.
  19. AndyPR

    AndyPR Senior Member

    All the samples that they need have been gathered, all they need now is enough funding to run the study, hopefully NIH will cough some up.
    Forbin, lauluce, acer2000 and 7 others like this.
  20. Undisclosed


    Please note some posts have been removed from this thread as they were either off-topic, contained defamatory statements or became no longer applicable as the thread was being cleaned up.

    Thank you.
    aimossy, Denise, Sushi and 1 other person like this.

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