I think I would separate out two parts of this post
FMT and being an FMT donor as an effective way to do good
Being an FMT donor as a means of earning money, hopefully to give
On the first, I would be a lot more hesitant about some of the claims that are being made. The evidence for FMT is young, and relatively weak. I think it is far from being a potential treatment of a broad range of chronic diseases; FMT is currently approved for recurrent C. difficile infection in the UK. Things we do not know:
Is it helpful for other chronic diseases? If so, how much and is it cost-effective?
Can it be safely administered at home? You make the claim that donation and use of FMT can happen outside of the hospital setting; this is currently not recommended.
Do we need super donors? There is a growing literature around the effectivneess of autologous FMT (use of your own stool for transplantation) may be as effective as a donation from someone else (one paper I am aware of, but I am sure there are many more). I would be hesitant in putting too much stock in one apprpoach early on in the R&D of this area.
On the second, I don’t have strong opinions. I think it is worth more explicitly flagging that a super donor is quite a rare statistical occurrence, and that the activation energy and cost to be accepted and donate stool for the first time might not make net positive from a cost-effectiveness perspective ( I have not modelled this, but I wouldnt be surprised if this was the case
Is it helpful for other chronic diseases? If so, how much and is it cost-effective?
I agree that there’s lots of unanswered questions, and plenty of theories to test. But we do have lots of data suggesting that FMT would be very helpful for other chronic diseases (http://HumanMicrobiome.info/Intro, http://HumanMicrobiome.info/FMT, etc.). I’m trying to get us to the next stage of demonstrating that it can be highly effective in humans for numerous conditions.
Regarding costs, I think cost-effectiveness is one area where FMT should shine. Stool is free, and currently has no value. The value derives from what the few extremely healthy people are willing to sell it for. The costs around FMT are mostly associated with finding donors, donor screening, storage, and shipping. I believe there have been a few papers looking at cost-effectiveness of FMT for C. diff, and finding it to be a good choice. https://www.ajmc.com/view/fmt-is-cost-effective-for-any-recurrent-clostridioides-difficile-infections-study-says
I believe that costs can be lowered even further by switching from a stool bank model to a “direct from donor” model. Yes, there are some cons, but I believe they are outweighed by the pros.
We started off selling a whole stool (10+ doses) for as little as $150. The only limitation was that we were unable to find the tiny percentage of “ideal donors”, for that price, and thus had to raise prices. We’re currently selling for $100 per dose, and doing means testing for low income people. I think this is plenty affordable, and most other sources of FMT are selling for 2-10x the price. Ultimately, it’s up to recipients/patients to determine if the costs are worth it. But so far, there are certainly many people willing to pay thousands of dollars (much more than we’re charging) merely for the potential to help their conditions. If FMT is demonstrated to be highly effective for many conditions, I have no doubt that people would be willing to pay tens of thousands for a high quality donor.
Can it be safely administered at home? You make the claim that donation and use of FMT can happen outside of the hospital setting; this is currently not recommended.
Naturally the medical community would not recommend people to perform a medical procedure on their own without supervision. There is certainly some merit to that, and we do recommend that patients get medical oversight from their doctor.
However, the actual procedure is extremely trivial (swallowing capsules, or performing an enema), and there is no need to have a doctor perform it. There are even downsides (delays, costs, colonoscopy risks, limited dosing, etc.) to having it performed as a medical procedure.
The primary difficulties with FMT are finding & screening a donor. It would be nice if doctors were able and willing to order the testing, but there are some restrictions with that, and most/all of the testing can typically be ordered online.
There is a growing literature around the effectivneess of autologous FMT (use of your own stool for transplantation) may be as effective as a donation from someone else (one paper I am aware of, but I am sure there are many more).
I would strongly disagree that autologous FMT has been shown to be similarly effective as FMT from a high quality donor. We have reports of 50% improvement for autism, and 90% of IBS patients improving.
I do not think aFMT is logically or scientifically supported by the current gut microbiome and FMT science (including much of what was referenced in the OP). I have an FAQ page here that provides some commentary and citations on aFMT: http://HumanMicrobiome.info/FAQ
This quote from the aFMT paper you linked actually supports my donor-quality hypothesis:
the microbiome of a healthy individual can deviate from an ``anti-inflammatory” (healthy) state to that of ``inflammatory” state of dysbiosis
In so far as what they’re considering “healthy” donors are actually not healthy. And they actually have dysbiotic, unstable gut microbiomes.
One of their other main arguments seems to be that an unhealthy gut microbiome (of the patient being treated) can sometimes be less dysbiotic. Yes, that’s certainly true. But I don’t think that supports using aFMT over FMT. An ideal donor should be much safer and more effective than using a “merely not sick”, or even a sick patient.
Another one of their main arguments is the lack of difference some studies show between aFMT and FMT. Again, my opinion is that they are merely demonstrating that their “healthy” donors are actually non-ideal donors.
I would say that FMTs are very safe to do at home. After all, you are just swallowing some pills or do an enema. The tricky part is donor screening for anything infectious. But it is easy to find out what to screen for and order the tests online or get a doctor to do them for you.
But yeah, doing these tests for the donor is absolutely necessary, and it can be dangerous if the donor isn’t thoroughly screened!
>Is it helpful for other chronic diseases? If so, how much and is it cost-effective?
I totally agree that the science isn’t settled yet at all! But please see the “Why aren’t scientists more excited…” section.
Also keep in mind that for many chronic diseases alternative effective treatments simply don’t exist yet, e.g. chronic fatigue syndrome, IBS, etc. Sure, the evidence on FMTs may not be conclusive. But it is at least suggestive. And that’s much better than nothing for many chronically ill. You don’t need “definite proof” to make it worth a try, given that it is fairly easy, safe, and cheap (if you know the donor and he just gives his stool to you) to do FMTs yourself!
Why am I not discouraged by poor outcomes in FMT studies.
FMTs look very promising, but there is by no means a clear scientific consensus on their efficacy. It’s an active area of research with many studies currently under way.
And while many scientists are very excited about FMTs, many studies actually yield very mixed results—with poor or no results being common. Anecdotal evidence on FMTs is also often not very convincing—with many recipients reporting no benefits.
However, I’m personally not discouraged by this, and indeed still excited about FMTs with good donors. The reason is that in my impression the vast majority of FMT studies and FMT self-experiments are flawed. Here’s why I believe this:
1. Poor donor quality.
Typical donor criteria you see in most FMT studies are severely deficient. The focus seems to be on choosing merely not sick donors, when it really should be about choosing exceptionally healthy donors with fantastic microbiomes. Most studies donor criteria’ are along the lines of “no antibiotics in the past 3 months, 18-50 yrs old, no viruses, infections, parasites, etc. in stool & blood test”. In short, if you are an overweight, depressed smoker who regularly eats fast food, you often still qualify as a donor in these studies. And even those studies who do actually try to find good donors that are actually healthy and fit, often don’t go nearly far enough—not least just because it is just extremely hard to find exceptionally good donors.
Find me a well-done study that uses donor criteria as described here and takes into account the points below—and if that study still shows only underwhelming results, then I’ll change my mind on this.
2. Oxygen exposure.
Your colon is an anaerobic environment, i.e. very low in oxygen. Thus, most bacteria and even more of the bacteriophages (which might be especially important for FMT efficacy) in stool are anaerobes. However, the vast majority of FMT studies does various processing like filtering, blending, etc. - all of which heavily oxygenates the stool sample, killing anaerobes, and thus very likely reducing efficacy. No wonder these studies show underwhelming results! What you want to do is to immediately vacuum seal the donated stools and suck the air out, and then do all the processing in an oxygen-free environment.
3. No fresh stool, but frozen
Freezing likely kills many of the bacteria and bacteriophages in the stool—very likely greatly reducing its efficacy. Ideally you’d use fresh stool that has been kArticlesept in a de-oxygenated vacuum bag. This is hard to do on a bigger commercial scale, but totally possible if you have your own donor living in the same city like you for DIY FMTs.
4. Inadequate treatment protocols
For example:
a) Insufficient treatment length. Many studies only do a single infusion, but for many people/conditions you might need to do it daily for 2+ months (Eg: ASU autism study).
b) Colon-only procedures. The small intestine is very important, so completely ignoring it is a likely flaw for some conditions. When doing FMTs, I’d always combine both the rectal and oral route for FMTs.
c) FMTs done in isolation, instead of synergistically with other treatments. It might well be that for some diseases, even well done FMTs from great donors might not be sufficient on their own, but when combined synergistically with many other positive microbiome interventions, they turn out to be the key ingredient to push the needle over the edge. Yet most studies don’t test for this.
Great post!
I think I would separate out two parts of this post
FMT and being an FMT donor as an effective way to do good
Being an FMT donor as a means of earning money, hopefully to give
On the first, I would be a lot more hesitant about some of the claims that are being made. The evidence for FMT is young, and relatively weak. I think it is far from being a potential treatment of a broad range of chronic diseases; FMT is currently approved for recurrent C. difficile infection in the UK. Things we do not know:
Is it helpful for other chronic diseases? If so, how much and is it cost-effective?
Can it be safely administered at home? You make the claim that donation and use of FMT can happen outside of the hospital setting; this is currently not recommended.
Do we need super donors? There is a growing literature around the effectivneess of autologous FMT (use of your own stool for transplantation) may be as effective as a donation from someone else (one paper I am aware of, but I am sure there are many more). I would be hesitant in putting too much stock in one apprpoach early on in the R&D of this area.
On the second, I don’t have strong opinions. I think it is worth more explicitly flagging that a super donor is quite a rare statistical occurrence, and that the activation energy and cost to be accepted and donate stool for the first time might not make net positive from a cost-effectiveness perspective ( I have not modelled this, but I wouldnt be surprised if this was the case
I agree that there’s lots of unanswered questions, and plenty of theories to test. But we do have lots of data suggesting that FMT would be very helpful for other chronic diseases (http://HumanMicrobiome.info/Intro, http://HumanMicrobiome.info/FMT, etc.). I’m trying to get us to the next stage of demonstrating that it can be highly effective in humans for numerous conditions.
Regarding costs, I think cost-effectiveness is one area where FMT should shine. Stool is free, and currently has no value. The value derives from what the few extremely healthy people are willing to sell it for. The costs around FMT are mostly associated with finding donors, donor screening, storage, and shipping. I believe there have been a few papers looking at cost-effectiveness of FMT for C. diff, and finding it to be a good choice. https://www.ajmc.com/view/fmt-is-cost-effective-for-any-recurrent-clostridioides-difficile-infections-study-says
I believe that costs can be lowered even further by switching from a stool bank model to a “direct from donor” model. Yes, there are some cons, but I believe they are outweighed by the pros.
We started off selling a whole stool (10+ doses) for as little as $150. The only limitation was that we were unable to find the tiny percentage of “ideal donors”, for that price, and thus had to raise prices. We’re currently selling for $100 per dose, and doing means testing for low income people. I think this is plenty affordable, and most other sources of FMT are selling for 2-10x the price. Ultimately, it’s up to recipients/patients to determine if the costs are worth it. But so far, there are certainly many people willing to pay thousands of dollars (much more than we’re charging) merely for the potential to help their conditions. If FMT is demonstrated to be highly effective for many conditions, I have no doubt that people would be willing to pay tens of thousands for a high quality donor.
Naturally the medical community would not recommend people to perform a medical procedure on their own without supervision. There is certainly some merit to that, and we do recommend that patients get medical oversight from their doctor.
However, the actual procedure is extremely trivial (swallowing capsules, or performing an enema), and there is no need to have a doctor perform it. There are even downsides (delays, costs, colonoscopy risks, limited dosing, etc.) to having it performed as a medical procedure.
The primary difficulties with FMT are finding & screening a donor. It would be nice if doctors were able and willing to order the testing, but there are some restrictions with that, and most/all of the testing can typically be ordered online.
I would strongly disagree that autologous FMT has been shown to be similarly effective as FMT from a high quality donor. We have reports of 50% improvement for autism, and 90% of IBS patients improving.
I do not think aFMT is logically or scientifically supported by the current gut microbiome and FMT science (including much of what was referenced in the OP). I have an FAQ page here that provides some commentary and citations on aFMT: http://HumanMicrobiome.info/FAQ
This quote from the aFMT paper you linked actually supports my donor-quality hypothesis:
In so far as what they’re considering “healthy” donors are actually not healthy. And they actually have dysbiotic, unstable gut microbiomes.
One of their other main arguments seems to be that an unhealthy gut microbiome (of the patient being treated) can sometimes be less dysbiotic. Yes, that’s certainly true. But I don’t think that supports using aFMT over FMT. An ideal donor should be much safer and more effective than using a “merely not sick”, or even a sick patient.
Another one of their main arguments is the lack of difference some studies show between aFMT and FMT. Again, my opinion is that they are merely demonstrating that their “healthy” donors are actually non-ideal donors.
I would say that FMTs are very safe to do at home. After all, you are just swallowing some pills or do an enema. The tricky part is donor screening for anything infectious. But it is easy to find out what to screen for and order the tests online or get a doctor to do them for you.
But yeah, doing these tests for the donor is absolutely necessary, and it can be dangerous if the donor isn’t thoroughly screened!
>Is it helpful for other chronic diseases? If so, how much and is it cost-effective?
I totally agree that the science isn’t settled yet at all! But please see the “Why aren’t scientists more excited…” section.
Also keep in mind that for many chronic diseases alternative effective treatments simply don’t exist yet, e.g. chronic fatigue syndrome, IBS, etc. Sure, the evidence on FMTs may not be conclusive. But it is at least suggestive. And that’s much better than nothing for many chronically ill. You don’t need “definite proof” to make it worth a try, given that it is fairly easy, safe, and cheap (if you know the donor and he just gives his stool to you) to do FMTs yourself!
Why am I not discouraged by poor outcomes in FMT studies.
FMTs look very promising, but there is by no means a clear scientific consensus on their efficacy. It’s an active area of research with many studies currently under way.
And while many scientists are very excited about FMTs, many studies actually yield very mixed results—with poor or no results being common. Anecdotal evidence on FMTs is also often not very convincing—with many recipients reporting no benefits.
However, I’m personally not discouraged by this, and indeed still excited about FMTs with good donors. The reason is that in my impression the vast majority of FMT studies and FMT self-experiments are flawed. Here’s why I believe this:
1. Poor donor quality.
Typical donor criteria you see in most FMT studies are severely deficient. The focus seems to be on choosing merely not sick donors, when it really should be about choosing exceptionally healthy donors with fantastic microbiomes. Most studies donor criteria’ are along the lines of “no antibiotics in the past 3 months, 18-50 yrs old, no viruses, infections, parasites, etc. in stool & blood test”. In short, if you are an overweight, depressed smoker who regularly eats fast food, you often still qualify as a donor in these studies. And even those studies who do actually try to find good donors that are actually healthy and fit, often don’t go nearly far enough—not least just because it is just extremely hard to find exceptionally good donors.
Find me a well-done study that uses donor criteria as described here and takes into account the points below—and if that study still shows only underwhelming results, then I’ll change my mind on this.
2. Oxygen exposure.
Your colon is an anaerobic environment, i.e. very low in oxygen. Thus, most bacteria and even more of the bacteriophages (which might be especially important for FMT efficacy) in stool are anaerobes. However, the vast majority of FMT studies does various processing like filtering, blending, etc. - all of which heavily oxygenates the stool sample, killing anaerobes, and thus very likely reducing efficacy. No wonder these studies show underwhelming results! What you want to do is to immediately vacuum seal the donated stools and suck the air out, and then do all the processing in an oxygen-free environment.
3. No fresh stool, but frozen
Freezing likely kills many of the bacteria and bacteriophages in the stool—very likely greatly reducing its efficacy. Ideally you’d use fresh stool that has been kArticlesept in a de-oxygenated vacuum bag. This is hard to do on a bigger commercial scale, but totally possible if you have your own donor living in the same city like you for DIY FMTs.
4. Inadequate treatment protocols
For example:
a) Insufficient treatment length. Many studies only do a single infusion, but for many people/conditions you might need to do it daily for 2+ months (Eg: ASU autism study).
b) Colon-only procedures. The small intestine is very important, so completely ignoring it is a likely flaw for some conditions. When doing FMTs, I’d always combine both the rectal and oral route for FMTs.
c) FMTs done in isolation, instead of synergistically with other treatments. It might well be that for some diseases, even well done FMTs from great donors might not be sufficient on their own, but when combined synergistically with many other positive microbiome interventions, they turn out to be the key ingredient to push the needle over the edge. Yet most studies don’t test for this.