Michael Harrop
Active member
I'm writing about your donor quality criteria. Virtually all FMT trials, stool banks, clinics, etc. are using low-quality donors. The current criteria for donor quality is completely inadequate. Why this is, I can only guess that the people in charge do not follow the literature closely, have a poor understanding of the gut microbiome's impacts on the entire body, and have a poor understanding of human health.
As is, the vast majority of FMT trials are simply a waste of time and money due to poor donor quality, and lack of comparison to high-quality donors. And this is delaying the period where high-quality, curative donors will be available for patients in desperate need of them.
What we need are FMT studies using people like these as donors:
And comparing each of their efficacy to a variety of people with different disease states (IBS, UC, obesity, etc.). To find out the outcomes of "is 'x' type of person a more effective donor for 'y' disease, while 'a' person more effective for 'b' disease, or is 'x' just moderately effective for many and 'a' is highly effective for many. Of course, there are other important factors (see below - abx, stool type, etc.), that vary from person to person regardless of "long-distance runner" vs "sprinter".
Below I will copy some information I've been sending around.
I would encourage you guys to look through this wiki, including the questionnaire: https://humanmicrobiome.info/fmt/
In short, my experiences with 9 donors (https://docs.google.com/document/d/1cagQpzRCa7Uy8QZYV6NiywDhPELBlzHxUk1OWPR3kNM), and feedback from lots of people over the years who did DIY FMT, strongly support only stool type 3 representing an intact, unperturbed, disease resistant gut microbiome. PLUS zero lifetime antibiotic use.
Below are excerpts from my conversations with an author on the FMT study that showed placebo group did better than FMT group for IBS. http://dx.doi.org/10.1136/gutjnl-2018-316434
In short, it's almost certainly a donor quality issue, and glycerol was used in the placebo, which could have had significant improvements on the IBS-C group since it is a laxative. Continued neglect for obtaining higher quality donors is harmful to patients by both the direct impacts of a low-quality donor, and by delaying actual treatment from a high-quality donor.
While the authors of this study went through considerable length to obtain high-quality donors (this guy for example: https://sputniknews.com/europe/201801121060696835-denmark-fecal-transplantation. 3 out of 700 = pass rate of 0.4%), they were unable to find anyone with zero-lifetime antimicrobial use and type 3 stool. The current standard for stool comp of bristol stool type 3 or 4 is not based on any data, but rather intuition. My extensive experiences and a substantial amount of feedback from others suggest this intuition is wrong. I am currently using a 9th donor who donates to a clinic in the US, has type 4 stool and lifetime antibiotic use, and the impacts are exactly as mild as I would expect. I have CFS and IBS-D.
Notice below that bowel cleansing gave symptom relief, which completely supports my position that low-quality donors are simply adding more of what we patients don't need - uncontrolled/dysbiotic microbial communities. It is vital to identify eubiotic, disease-resistant gut microbiomes in donors, and current donor criteria fail to do this.
These are the strategies I can think of to find the best donors:
Contact university dean(s) & president, and athletics & biology departments. The former should be able to send a notice out to all students, and the latter would have the ability to give direct access to some of the most likely sources of high-quality donors - young, top athletes. Sprinters seem to have some of the best candidates.
Youth athletic venues, professional and amateur athletic organizations including Olympic and dance, various fitness centers like rock climbing, etc..
Grip Strength Is Associated With Cognitive Performance in Schizophrenia and the General Population: A UK Biobank Study of 476559 Participants https://doi.org/10.1093/schbul/sby034
Hand Grip Strength as a Clinical Biomarker for ME/CFS and Disease Severity (2018): https://www.frontiersin.org/articles/10.3389/fneur.2018.00992/full
My own grip strength decreases along with my general health, and increases when my health does. I think grip strength has good potential to be a donor quality measurement.
Muscle mass should be a new vital sign, research shows. Implications of low muscle mass across the continuum of care: a narrative review (2018) https://www.eurekalert.org/pub_releases/2018-10/ghn-mms101718.php
"reaction time being a more relevant measure of cognitive ability vis-à-vis the microbiome" (2018): https://www.frontiersin.org/articles/10.3389/fnagi.2018.00398/full
--------Below is copied from my emails with one of the study authors------
A bacterium exposed to a phage & an antibiotic achieved higher levels of phage resistance compared to populations exposed to the phage alone. In addition, the phage became extinct under co-selection while remaining present in the phage-alone environment (2016): https://onlinelibrary.wiley.com/doi/abs/10.1111/mec.13950
The results make sense if you consider phages. If a low-quality gut microbiome has a chaotic phageome as described here: https://web.archive.org/web/20230610072550/https://old.reddit.com/r/HumanMicrobiome/comments/92d5zw/viral_microbiome_changes_could_be_an_underlying/ - then a low-quality donor would be adding to the problem (of overabundant bacteria who have no phages to control them).
Since phages are the natural method whereby bacterial populations are kept in check and not allowed to "overgrow", then a microbiome without the needed phages would be in a state of dysbiosis, and the bacteria would be harmful. Thus you would be implanting exactly the opposite of what the FMT patients need - many would need phages whereas you're giving them uncontrolled bacterial populations.
There is significant evidence that phages play a major role in the gut microbiome and FMT. See: https://humanmicrobiome.info/#bacteriophages-phages
There is evidence that antimicrobials do permanent damage to the immune system, possibly not even fully recoverable via FMT: https://genome.cshlp.org/content/20/10/1411.long
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5395657/
One of the primary causes of IBS seems to be problems with bile acid metabolism/absorption (which is a process mediated by gut microbes): https://humanmicrobiome.info/bile/
And you can see in that link that FMT success is also linked to changing the bile acid metabolism. Not every donor can successfully change the patient's bile acid metabolism to an ideal state, so this is where donor quality comes into play again.
I have IBS-D caused by Rifaximin (antibiotic) and Cholestyramine (bile acid sequestrant) is massively helpful for me, and many others with IBS-D. And one specific FMT donor was able to fix my bile acid metabolism, allowing me to eat fat again without needing the bile acid sequestrant.
Moreover, I am extremely convinced that zero-lifetime antimicrobial use plus consistent type 3 stools (regardless of what they eat) are essential qualities of a highly effective donor: https://docs.google.com/document/d/1cagQpzRCa7Uy8QZYV6NiywDhPELBlzHxUk1OWPR3kNM
The knowledge of your donors only adds to this.
Of course not every type 3 stool is healthy, it will vary from person to person. But my current thinking is that "all high-quality donors are type 3, but not every type 3 donor is high quality". See Anna Karenina hypothesis: https://www.theatlantic.com/science/archive/2017/08/a-grand-unified-theory-of-unhealthy-microbiomes/537945/ “All happy families are alike; each unhappy family is unhappy in its own way.”
The bowel cleansing apparently gives symptom relief. Adding new bacteria right away (FMT), will counteract this effect.
Another theory:
A lot of people are simply eating too much junk and drinking too many sweet beverages.
If our patients were living on fast and processed food and downing it with coca cola, the new microorganisms would not survive a day. We were not allowed to make more than one intervention so we did not talk to them about diet.
About the type 3 or 4 donor-stool:
Our donors do produce type 4 about 90% of the time
Original 06 Nov 2018 (3 comments).
As is, the vast majority of FMT trials are simply a waste of time and money due to poor donor quality, and lack of comparison to high-quality donors. And this is delaying the period where high-quality, curative donors will be available for patients in desperate need of them.
What we need are FMT studies using people like these as donors:
- https://www.worldathletics.org/news/news/world-championships-doha-2019-usa-team
- https://www.youtube.com/playlist?list=PLfKZiZbk2tkYU3kA2Czy9goMofrL1XxMP
- https://www.youtube.com/watch?v=5qIPZrwnQak
And comparing each of their efficacy to a variety of people with different disease states (IBS, UC, obesity, etc.). To find out the outcomes of "is 'x' type of person a more effective donor for 'y' disease, while 'a' person more effective for 'b' disease, or is 'x' just moderately effective for many and 'a' is highly effective for many. Of course, there are other important factors (see below - abx, stool type, etc.), that vary from person to person regardless of "long-distance runner" vs "sprinter".
Below I will copy some information I've been sending around.
I would encourage you guys to look through this wiki, including the questionnaire: https://humanmicrobiome.info/fmt/
In short, my experiences with 9 donors (https://docs.google.com/document/d/1cagQpzRCa7Uy8QZYV6NiywDhPELBlzHxUk1OWPR3kNM), and feedback from lots of people over the years who did DIY FMT, strongly support only stool type 3 representing an intact, unperturbed, disease resistant gut microbiome. PLUS zero lifetime antibiotic use.
Below are excerpts from my conversations with an author on the FMT study that showed placebo group did better than FMT group for IBS. http://dx.doi.org/10.1136/gutjnl-2018-316434
In short, it's almost certainly a donor quality issue, and glycerol was used in the placebo, which could have had significant improvements on the IBS-C group since it is a laxative. Continued neglect for obtaining higher quality donors is harmful to patients by both the direct impacts of a low-quality donor, and by delaying actual treatment from a high-quality donor.
While the authors of this study went through considerable length to obtain high-quality donors (this guy for example: https://sputniknews.com/europe/201801121060696835-denmark-fecal-transplantation. 3 out of 700 = pass rate of 0.4%), they were unable to find anyone with zero-lifetime antimicrobial use and type 3 stool. The current standard for stool comp of bristol stool type 3 or 4 is not based on any data, but rather intuition. My extensive experiences and a substantial amount of feedback from others suggest this intuition is wrong. I am currently using a 9th donor who donates to a clinic in the US, has type 4 stool and lifetime antibiotic use, and the impacts are exactly as mild as I would expect. I have CFS and IBS-D.
Notice below that bowel cleansing gave symptom relief, which completely supports my position that low-quality donors are simply adding more of what we patients don't need - uncontrolled/dysbiotic microbial communities. It is vital to identify eubiotic, disease-resistant gut microbiomes in donors, and current donor criteria fail to do this.
These are the strategies I can think of to find the best donors:
Contact university dean(s) & president, and athletics & biology departments. The former should be able to send a notice out to all students, and the latter would have the ability to give direct access to some of the most likely sources of high-quality donors - young, top athletes. Sprinters seem to have some of the best candidates.
Youth athletic venues, professional and amateur athletic organizations including Olympic and dance, various fitness centers like rock climbing, etc..
Grip Strength Is Associated With Cognitive Performance in Schizophrenia and the General Population: A UK Biobank Study of 476559 Participants https://doi.org/10.1093/schbul/sby034
Hand Grip Strength as a Clinical Biomarker for ME/CFS and Disease Severity (2018): https://www.frontiersin.org/articles/10.3389/fneur.2018.00992/full
My own grip strength decreases along with my general health, and increases when my health does. I think grip strength has good potential to be a donor quality measurement.
Muscle mass should be a new vital sign, research shows. Implications of low muscle mass across the continuum of care: a narrative review (2018) https://www.eurekalert.org/pub_releases/2018-10/ghn-mms101718.php
"reaction time being a more relevant measure of cognitive ability vis-à-vis the microbiome" (2018): https://www.frontiersin.org/articles/10.3389/fnagi.2018.00398/full
--------Below is copied from my emails with one of the study authors------
ME:
I know phage research is really in its infancy, but the one study I saw about phages & antibiotics suggests antibiotic damage to the phageome is likely severe and underappreciated at the moment:A bacterium exposed to a phage & an antibiotic achieved higher levels of phage resistance compared to populations exposed to the phage alone. In addition, the phage became extinct under co-selection while remaining present in the phage-alone environment (2016): https://onlinelibrary.wiley.com/doi/abs/10.1111/mec.13950
The results make sense if you consider phages. If a low-quality gut microbiome has a chaotic phageome as described here: https://web.archive.org/web/20230610072550/https://old.reddit.com/r/HumanMicrobiome/comments/92d5zw/viral_microbiome_changes_could_be_an_underlying/ - then a low-quality donor would be adding to the problem (of overabundant bacteria who have no phages to control them).
Since phages are the natural method whereby bacterial populations are kept in check and not allowed to "overgrow", then a microbiome without the needed phages would be in a state of dysbiosis, and the bacteria would be harmful. Thus you would be implanting exactly the opposite of what the FMT patients need - many would need phages whereas you're giving them uncontrolled bacterial populations.
There is significant evidence that phages play a major role in the gut microbiome and FMT. See: https://humanmicrobiome.info/#bacteriophages-phages
There is evidence that antimicrobials do permanent damage to the immune system, possibly not even fully recoverable via FMT: https://genome.cshlp.org/content/20/10/1411.long
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5395657/
One of the primary causes of IBS seems to be problems with bile acid metabolism/absorption (which is a process mediated by gut microbes): https://humanmicrobiome.info/bile/
And you can see in that link that FMT success is also linked to changing the bile acid metabolism. Not every donor can successfully change the patient's bile acid metabolism to an ideal state, so this is where donor quality comes into play again.
I have IBS-D caused by Rifaximin (antibiotic) and Cholestyramine (bile acid sequestrant) is massively helpful for me, and many others with IBS-D. And one specific FMT donor was able to fix my bile acid metabolism, allowing me to eat fat again without needing the bile acid sequestrant.
Moreover, I am extremely convinced that zero-lifetime antimicrobial use plus consistent type 3 stools (regardless of what they eat) are essential qualities of a highly effective donor: https://docs.google.com/document/d/1cagQpzRCa7Uy8QZYV6NiywDhPELBlzHxUk1OWPR3kNM
The knowledge of your donors only adds to this.
Of course not every type 3 stool is healthy, it will vary from person to person. But my current thinking is that "all high-quality donors are type 3, but not every type 3 donor is high quality". See Anna Karenina hypothesis: https://www.theatlantic.com/science/archive/2017/08/a-grand-unified-theory-of-unhealthy-microbiomes/537945/ “All happy families are alike; each unhappy family is unhappy in its own way.”
HIM:
My personal idea why the placebo group did better in the trial:The bowel cleansing apparently gives symptom relief. Adding new bacteria right away (FMT), will counteract this effect.
Another theory:
A lot of people are simply eating too much junk and drinking too many sweet beverages.
If our patients were living on fast and processed food and downing it with coca cola, the new microorganisms would not survive a day. We were not allowed to make more than one intervention so we did not talk to them about diet.
About the type 3 or 4 donor-stool:
Our donors do produce type 4 about 90% of the time
Original 06 Nov 2018 (3 comments).