1. Guest, the 'News in Brief' for the week beginning 29th June 2020 is here.
    Dismiss Notice
  2. Welcome! To read the Core Purpose and Values of our forum, click here.
    Dismiss Notice
  3. Guest, the DecodeME study has announced £3.2m of funding, click here to read about it.
    Dismiss Notice

Who to contact to get an FMT clinical trial with high quality donors? Poor donor quality is likely what's keeping this from being an available cure

Discussion in 'Advocacy Projects and Campaigns' started by MaximilianKohler, Apr 6, 2019.

  1. MaximilianKohler

    MaximilianKohler Established Member

    Messages:
    17
    Likes Received:
    27
    I've been following the microbiome literature daily for 4+ years while cataloging it all into this wiki: https://old.reddit.com/r/HumanMicrobiome/wiki/

    There is tremendous support for FMT being close to a panacea with the major caveat being that the donor is in perfect health, with an unperturbed, disease-resistant, curative gut microbiome. It's currently looking like fewer than 0.4% of the population qualifies: https://archive.fo/JmcMV#selection-1525.120-1525.121

    I've done DIY FMTs from 9 different donors, published my detailed results and lessons: https://docs.google.com/document/d/1cagQpzRCa7Uy8QZYV6NiywDhPELBlzHxUk1OWPR3kNM/, and shared it with hundreds of researchers.

    First I emailed all 180 authors running current FMT clinical trials https://archive.fo/YZ7Xk#selection-1603.11-1607.1 to complain about, and advocate for higher donor quality. Then I emailed dozens more USA-based IBS and CFS researchers who were authors on papers listed in the wiki to see if they'd be able to run an FMT clinical trial with high quality donors. I emailed the major microbiome research centers in California. I emailed CFS and IBS advocacy groups to ask who I should contact. A journal editor advised me to contact American Gasto Assoc authors on IBS guidelines, and US authors on the Rome Foundation IBS guidelines - same for the CFS researchers. I did that as well and still no takers.

    From my view, anyone in a position to do something about it has their head up their ass. Among professionals involved in FMT/microbiome there seems to be a large amount of ignorance, apathy, myopic focus on one tiny piece of the puzzle, and resistance to reviewing relevant information and investigating its merit. There might be a few researchers who are the exception, but they don't seem to have the capability to run a clinical trial.

    I'm so sick of this. There's likely a cure right now, and it's easy as hell to obtain, given the right people try to obtain it.

    I contacted the Norweigian guys doing a CFS FMT study to share info on what makes a high quality donor and urged them to find one. I don't know if they bothered to do so and we won't find out till 2023 - when the study ends. I'm not waiting around.

    I'm going to start writing to newspapers now.
     
    Peter Trewhitt and hinterland like this.
  2. Trish

    Trish Moderator Staff Member

    Messages:
    23,601
    Likes Received:
    116,722
    Location:
    UK
    Hi @MaximilianKohler. I'm sorry I don't have the energy to read through all your documents. Can you summarise in a few sentences what you think you know that the scientists researching FMT are missing.
     
  3. arewenearlythereyet

    arewenearlythereyet Senior Member (Voting Rights)

    Messages:
    1,916
    Likes Received:
    13,917
    Is it possible that we don’t know enough yet about what healthy looks like to do a rigorous clinical trial ?

    I also follow the scientific literature on gut biome and I think that we are miles off knowing anything ...a lot of the papers published are poor science with poor methodology and have extremely fanciful leaps of faith which seems to be the norm nowadays (normally for securing funding or just plain ignorance or as a way of raising profile or a mixture of all 3).

    You normally find this in any field of research but this is especially prevalent at the beginning of research into a field that’s in its infancy. I don’t think we have scratched the surface of what’s going to know anything beyond the variation that’s a result of variation in the human diet. Proposed generic causal links with disease or obesity are extremely dubious and mainly wishful thinking at this stage of our understanding.

    I think most of the research to date doesn’t really show much so I’m curious as to what you have spotted. I can’t read through lots ..so have to break things down into prioritised bite sized chunks. Apologies I haven’t attempted your link.

    Apologies in advance i may require a week to reply to anything you say I’ve posed questions mainly to tease out some more info so you get a decent discussion going. Many here will be like myself and not be able to digest too much in one go.
     
    sea, Rosie, oldtimer and 5 others like this.
  4. MaximilianKohler

    MaximilianKohler Established Member

    Messages:
    17
    Likes Received:
    27
    FMT is only effective if the donor is in perfect health, with an unperturbed, disease-resistant, curative gut microbiome. Most people involved in the gut microbiome & FMT do not seem to understand this notion. They do not seem to have a good understanding of human health and the gut microbiome's impacts on the entire body.

    Also, I figured out that very likely the characteristics of a high quality ("super donor") donor is 0 lifetime antimicrobial use, consistent type 3 stools regardless of what they eat, and ideal answers on this questionnaire that is vastly more detailed than what's currently being used: https://archive.fo/s3Uwx

    I think the people in positions of power in the microbiome/FMT world indeed do not know enough. But I believe I have this missing insight, and I think I've developed a very strong hypothesis regarding the qualities of a high quality donor, and I've sent that info to hundreds of researchers. Now all we need is for one of them to test my hypothesis in a clinical trial.

    Regarding causal links, there are numerous papers proving causation, and I've tried to catalogue them in the reddit sub. All FMT studies show causation, and there have been many. You can use the "FMT" and "causation" flairs in the sidebar to sort/find some:

    FMT: https://old.reddit.com/r/humanmicrobiome/search?q=flair:'FMT'&sort=new&restrict_sr=on
    Causation: https://old.reddit.com/r/humanmicrobiome/search?q=flair:'Causation'&sort=new&restrict_sr=on

    And others are listed in the wiki, including sections like "mechanisms" here: https://old.reddit.com/r/HumanMicrobiome/wiki/intro
     
  5. Trish

    Trish Moderator Staff Member

    Messages:
    23,601
    Likes Received:
    116,722
    Location:
    UK
    I'm pretty sure people in the FMT medical world are perfectly well aware that they should get as 'clean' as donor as possible, but if you're treating people with severe unresolved clostridium difficile infection, you get the best donors available. I have not come across any credible claim backed up by double blind trial research that FMT is curative for anything else. Can you point us to some?

    Are you a researcher with access to the proper lab facilities for your experiments, and, if so, can you point to the clinical trials you are involved in?

    If not, then it seems to me that whatever you are claiming is no more than anecdote, second hand information and speculation. Nothing wrong with that, so long as you make it clear that's what it is.
     
  6. MaximilianKohler

    MaximilianKohler Established Member

    Messages:
    17
    Likes Received:
    27
    All the current evidence says they are not.

    Beyond the info I shared in the OP, here are more:
    https://archive.fo/tk0wM

    Mar 2019 study showing Openbiome donors are causing IBS in 30% of patients: https://archive.fo/eIm25 - nowhere in Openbiome's public safety reports is this mentioned. The study is looking at why patients are getting IBS after FMT, and they're looking at everything other than donor quality. They seem so intent on ignoring donor quality.

    31 patients were given FMTs from a pre-Crohn's donor. (Jan 2019): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423689/

    There has been no efforts that I'm aware of to find high quality donors. As far as I know Openbiome only attempts to recruit donors from a nearby gym despite being in close proxy to world class universities with likely dozens of extremely healthy, well functioning people who would be high quality donors. I have written to them about this, and as far as I can tell both them and their research partners continue to ignore donor quality.

    Additionally, the trust shown to "professionals" is naive. There are major problems with our medical and research systems where a large majority of them are poorly informed on their own field and related ones: https://archive.fo/dRePn



    Firstly, it seems like only low quality donors are available to them due to apathy. Secondly, Openbiome has been providing stool for clinical trials for way more things than c.diff. Thirdly, this low donor quality issue pervades every single entity providing FMT, and a large number of them are doing clinical trials for things other than c.diff.

    This is exactly what this thread is about. Getting that trial done. Current trials are all using low quality donors and thus wasting huge amounts of time and money, endangering patients, and drastically delaying the point when a cure/treatment is available.


    I am not, otherwise I wouldn't need to make this thread.


    I understand that us CFS people have low brain function and thus reading a bunch of stuff is hard. But there is a golden rule - to not take authoritative stances on things a person has not read/became fully informed on. It's very frustrating to see people do that. I provided a large amount of info in the OP and I would appreciate it if people would refrain from taking firm, uninformed stances without reviewing it all.
     
  7. NelliePledge

    NelliePledge Moderator

    Messages:
    5,030
    Likes Received:
    33,491
    Location:
    UK West Midlands
    If you’re not going to make the effort to communicate in a way that’s accessible to people why would they make any effort to possibly over exert themselves by reading your large amount of information.....
     
  8. Trish

    Trish Moderator Staff Member

    Messages:
    23,601
    Likes Received:
    116,722
    Location:
    UK
    I do understand your frustration, I have had a look at some of the documents you link to and you have clearly put a huge amount of work into collecting and collating documents, and writing about your own experience. However, that doesn't necessarily mean you know something scientists researching the gut microbiome don't know.

    Do I understand correctly that you are working from the premise that FMT is the cure-all for everything, and that that the key is that donors have to fit your definition of 'pure' for it to succeed? And you have set yourself on a so far unsuccessful mission to persuade people researching the gut microbiome that if only they followed your guidance, they would be able to cure everything?

    I apologise if I have misunderstood your mission. Do explain if I am wrong.
     
    adambeyoncelowe, Wonko and Cheshire like this.
  9. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

    Messages:
    7,011
    Likes Received:
    71,276
    The chances that a completely healthy donor is the best donor for any particular situation seem to me to be close to zero. One would expect some sort of health imbalance to lead, by chance, to an increase in the 'really good' bacteria.

    Since nobody knows what happens with optimal donors and so we cannot know who they are I cannot see quite where you are going with this.

    In the context of ME/CFS we do not even have either a rationale for faecal transplant or evidence it would ever be of any use.
     
  10. MaximilianKohler

    MaximilianKohler Established Member

    Messages:
    17
    Likes Received:
    27
    I have no idea how you could read what I've written and linked here and then imply that I'm not making an effort. Additionally, I have no idea what your idea of an optimal communication method is.

    I think the wording you chose is flawed/misleading. It's not simply a "premise" but a fairly well supported hypothesis with a variety of strong supporting evidence. However, that evidence comes in many forms and thus takes some time to go through it all. Anyone working in the microbiome/FMT field should be familiar with it, but unfortunately due to the egregious shortcomings I mentioned, most do not seem to be. Furthermore, it requires some knowledge/intelligence/intuition outside of the microbiome field.


    This is an extremely disappointing statement to read. In my opinion no one who is up to date with the microbiome research and has a good understanding of human health and the gut microbiome's impact on the entire body would ever make a statement like that.

    I cannot make sense of this statement.

    This is simply completely false. If you were right there wouldn't be an ongoing FMT clinical trial for CFS.

    I once again reference the golden rule I mentioned earlier.

    I wonder why a person so clearly not informed on this would make such an authoritative statement that serves to hinder the procurement of a treatment/cure for the condition which this entire site is based on trying to cure? I don't know if you're just dragged down into despair and excess pessimism, but what you're doing is harmful to all of us.

    It's also very odd and disappointing to see such statements on a site titled "science for ME".
     
  11. Trish

    Trish Moderator Staff Member

    Messages:
    23,601
    Likes Received:
    116,722
    Location:
    UK
    I read a short book some time ago by someone who was convinced that the ideal FMT donor would be from an isolated tribe living on a mostly plant based diet unpolluted by Western refined foods. He experimented on himself, but he did at least get their poo checked for nasty diseases first, and he took samples to have his own microbiome tested before and afterwards.

    As far as I remember the balance of microorganisms reverted once he was back on a Western diet. In other words, unless you are using FMT to try to crowd out a pathogen such as C. Diff, it seems that changing the diet is a key factor in changing the balance of gut microorganisms, and the effect of FMT is likely to be temporary.

    There seems to be a lot of interest in 'leaky gut' hypotheses for ME and other conditions. So far it is at the unproven hypothesis stage, so a long way to go before talking of treatment. And when and if it does reach that stage a long way to go to whether FMT, diet or other approaches are relevant.
    .......

    On the subject of communicating ideas effectively with forum members I have 2 simple suggestions.

    1. Present a summary of the key points in a post with a short description of the evidence it is based on. Don't expect members to have either the time, energy or interest in reading all the material you have accumulated over years.

    2. Scientific ideas based on reading and personal experience are best presented as ideas for discussion, not as dogmatic claims to truth. We can't know if our ideas are right if they haven't been subjected to rigorous scientific testing.

    One of the scientists presenting a talk at a recent ME conference reminded the audience that a good scientist does their level best to test their theory to destructon, carrying out every experiment they can think of to try to disprove their hypothesis. Only then can they claim the evidence supports the hypothesis. And even then, it is a well supported hypothesis, not an immutable fact.
     
  12. Wonko

    Wonko Senior Member (Voting Rights)

    Messages:
    3,851
    Likes Received:
    28,164
    Location:
    UK
    3. Define 'healthy' as no one else seems able to.

    As far as I can see it's only possible to define healthy in terms of a single individual, so what would be a healthy microbiome in one person could easily be dysfunctional in another, for obvious reasons. And ATM nothing I've seen suggests they can even do that. They can tell general patterns, they can identify some species, but anything beyond that, they haven't a clue.

    How, in that context, can 'healthy', even for a single individual, possibly be established? And if that can't be done, yet, how could 'healthy' donors possibly be achieved?

    The absolutely most that could be said is that a particular donor's microbiome is likely to be 'unhealthy', and even that's a problematic assumption as they don't know how the system is supposed to work, ATM they only seem to be at the level of assessing diversity, of species, and assuming that more species is better.
     
  13. Dr Carrot

    Dr Carrot Senior Member (Voting Rights)

    Messages:
    259
    Likes Received:
    2,525
    Please just understand that if you aggressively and dogmatically push your own hypothesis, then you’re going to get pushback.

    I have plenty of ideas about what’s causative in CFS, but I can’t prove any of them, so I don’t say that they are correct. You’ve done a lot of research which is fantastic, I’d just hope that you’re more open to having your ideas critiqued in a non-personal, dispassionate way, based on the science. I think we are all in favour of more diverse research in CFS, so discussion and collaboration is to be encouraged.
     
    Last edited by a moderator: Apr 7, 2019
    Snowdrop, Cheshire, Hutan and 5 others like this.
  14. MaximilianKohler

    MaximilianKohler Established Member

    Messages:
    17
    Likes Received:
    27
    Yes, some people believe this, but it's not necessarily the case. Tribal health varies significantly from one tribe to another. They also might be carrying various pathogens.

    The discussion section of this 2014 review paper "Rural and urban microbiota - To be or not to be?" provides excellent info on gut microbiome, FMT, and donor selection: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4153773/

    The limitations of current testing capabilities means that testing cannot be relied upon for either safety nor efficacy. So any screening he did was very preliminary.

    I know that a researcher did a single DIY FMT from the Hadza while he was studying them and saw a similar shift.

    There could be numerous reasons for this, including that he only did an enema and thus missed the upper digestive system, and he only did a single FMT when it might require many over a long period of time.

    This is misinformation. I reference the wiki in the OP, including the "FMT" and "diet" sections: https://old.reddit.com/r/HumanMicrobiome/wiki/index#wiki_diet.3A - which shows diet has severe limitations, and FMT can result in long-term changes.

    Additionally, the "testing" section of the wiki shows there are severe limitations to current capabilities, and thus any study showing "change" or "no change" needs to be taken with a huge grain of salt.

    Additionally, since you did not cite your reference we can't look into the details of the study.



    I agree that it's in the hypothesis stage. I do not agree that it's a long way to go before a stage to find out whether FMT or other approaches are relevant. I reference this page: https://old.reddit.com/r/HumanMicrobiome/wiki/intestinalpermeability - which is only a small amount of the current literature on intestinal permeability (there's more in other parts of the wiki), but in my opinion gives enough preliminary evidence that:

    1. Permeability is likely a significant factor in many diseases where the gut microbiome is causing systemic impacts.
    2. FMT should be tested in a clinical trial to correct permeability.



    I tried to do that previously, but I welcome people to ask more questions. Additionally, the amount of supporting evidence is vast, so I'm not sure I can do much about that part.

    My hypotheses are based on a lot more than personal experience. Getting them subjected to rigorous scientific testing is what this thread is all about.


    Agree. This is why we need this clinical trial. It's the only way, short of us finding a super-donor on our own and hundreds of people using them, to find out if my hypothesis is correct.

    0 lifetime antimicrobial use, consistent type 3 stools regardless of what they eat, extremely physically fit, intelligent, happy, and other ideal answers on this questionnaire: https://archive.fo/s3Uwx


    The reasons do not seem obvious to me. In my detailed experiences & lessons document I cite the Anna Karenina hypothesis, which says:

    A Grand Unified Theory of Unhealthy Microbiomes. The Anna Karenina hypothesis says that every unbalanced microbiome is unbalanced in its own way. “All happy families are alike; each unhappy family is unhappy in its own way.” https://archive.fo/WP0Vb

    In my opinion, most of the current evidence supports this.


    Mostly correct.

    You are right. And this is something I've been complaining about. It seems that most current researchers have been trying to use primarily testing, which you accurately describe as extremely limited, to determine donor safety and efficacy. What I argue is that we need a more holistic view of things we already know about human health which have been established separately from our knowledge of the microbiome, and thus a detailed questionnaire like this one becomes one of the primary screening tools: https://archive.fo/s3Uwx

    I elaborated further with more examples in the google doc in the OP.



    There is nothing dogmatic about what I'm doing. I'm the one here, and there, with the tremendous amount of supporting evidence that no one bothers to review prior to making authoritative, contrary statements. No one has cited contrary evidence. So statements like that seem to be projection.

    Regarding PR moderation, they have extremely strict guidelines on anything that can remotely be considered rude. I definitely lack the brain capacity to sugar coat my statements, and typically use laconic sentences. People often interpret that as rude. I also find it frustrating when people make authoritative statements on things they are ignorant on. It spreads misinformation, which can be extremely harmful.



    Absolutely I am. I always welcome evidence-based discussions/debates.
     
    Last edited by a moderator: Apr 7, 2019
    Wonko likes this.
  15. adambeyoncelowe

    adambeyoncelowe Senior Member (Voting Rights)

    Messages:
    2,099
    Likes Received:
    14,840
    Just because something is published, does not necessarily make it true. Even peer-reviewed science isn't necessarily 'true' nor should it always be taken as fact.

    There can be flaws in methodology, or a lack of follow-up, or a failure to publish negative or null results.

    Also, we can be pretty sure one model of the way things are is right (such as a flat earth) before new science changes our perspective.

    I'm not yet convinced that the science behind FMT is there. We need large-scale RCTs with objective, consistent and reliable measures of benefit before we can make bold claims of it being a 'panacea' (even 'close to' one)--and I'm naturally sceptical of such claims.
     
  16. Cheshire

    Cheshire Moderator Staff Member

    Messages:
    3,672
    Likes Received:
    20,363
    Not implying that people who disagree with you are not intelligent enough, naïve or that what they say is systematically misleading would be good start. Just saying.
     
    sea, Wonko, adambeyoncelowe and 2 others like this.
  17. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

    Messages:
    7,011
    Likes Received:
    71,276
    Dear @MaximilianKohler,

    We would all like to be right about things but sometimes it is worth standing back and looking at the wider perspective.

    You seem to be the one making the dogmatic positive statements here. I am simply expressing scepticism.

    Do I know about this field? Well a few months back the UK Medical Research Council set up an advisory board on research strategy into ME/CFS. They invited three people to guide them on choice of research projects. Those three people were Maureen Hanson, Derya Unutmaz and myself. So at least the MRC seems to think I know a bit about the wider context of this.

    Maureen and some other groups have been doing speculative work into the possible role of microbiota in ME but nobody has any very clear theory as to why it should be relevant. The evidence that it is relevant is zero so far.

    That at least is my understanding from attending conferences and reading the literature. If you want to claim otherwise I am very eager to hear evidence but it has to be something plausible and reliably obtained.

    But maybe we should get back to your main claim - that we need completely healthy donors. Why?That sounds intuitively sensible at first but it cannot be based on any evidence if we have no results from trials to confirm it. Moreover, if you think a bit more it must be very likely that the ideal mix of bacteria for ME, if there is such a thing, is going to occur in rather unusual conditions where for some reason the 'best' bacteria are more prevalent than usual. In fact the logical conclusion would be that the ideal transplant would be an entirely artificial mix made up in the lab based on what had proven to be the best from trials. It is highly implausible that there is such a thing as a 'healthy balanced microbiome'.
     
    Barry, TrixieStix, Rosie and 7 others like this.
  18. Sly Saint

    Sly Saint Senior Member (Voting Rights)

    Messages:
    4,688
    Likes Received:
    39,167
    Location:
    UK
    hinterland, adambeyoncelowe and Trish like this.
  19. arewenearlythereyet

    arewenearlythereyet Senior Member (Voting Rights)

    Messages:
    1,916
    Likes Received:
    13,917
    I had a quick skim of the super donor article. Here is my summary for those unable to read etc.

    In summary:

    They think (although there is little conclusive proof) that a wide variety of species within gut flora is a good thing and pooling stools (an expression that i find quite unsavoury) from a wide variety of donors is the better course of action rather than using carefully isolated super donors. The premise being ...we don’t really know what’s going on so if we throw the kitchen sink at it (I’m terms of lots of species) it should sort itself out better than trying to force a super donor flora onto an indivdual when we know that flora varies a lot between healthy individuals.

    What the article skims over is the cause or effect argument ....basically it acknowledges that cause is difficult to prove since we don’t know enough but then goes on to say that the plethora of small inconclusive studies that suggest a cause is sufficient. It reads a bit contradictory in places.

    That’s my take on it ...personally I find this ‘leap of faith science” rather non scientific...but I am old school I suppose.

    My suspicion is that it is highly unlikely that there is one perfect human gut flora that is composed of hundreds or thousands of species. There is probably many many combinations that make a person “healthy”.
     
    sea, Hutan, TrixieStix and 8 others like this.
  20. Jonathan Edwards

    Jonathan Edwards Senior Member (Voting Rights)

    Messages:
    7,011
    Likes Received:
    71,276
    Yes, I remember this paper being flagged up on a thread a while back. I agree that it all seems to be speculation from intuition rather than evidence based science.
     

Share This Page