FMT roadmap proposal

1. Find one or more donors with consistent type 3 stool (dark, small, firm, dry), 0 lifetime antimicrobial use, peak physical and mental health, and other ideal questionnaire answers. Test them in a clinical trial for one or more conditions such as IBS, CFS, IBD. From this we should be able to get some idea of how that quality donor compares with the current quality. In my opinion we should be doing simultaneous oral and rectal FMT administration already, in addition to at least 10 FMTs per person.

I believe my "dark type 3 stools hypothesis" could be verified via bile acid metabolism profiling. As I believe a deficiency in bile acid metabolism (missing microbes) is a primary cause of other stool types [1].

 

If possible, test different types of donors in this step, such as "sprinter vs marathon runner". If we can't do that in this same step, then do that next. See if sprinter is more effective for certain conditions and marathon runner more effective for others, or is one generally more effective than the other, and if mixed is that even better.

    2. After that, we can move on to test things like "if the recipients liquid fast for 1-5 days prior does that increase efficacy" [1]. Could also test liquid fasting while doing FMTs. The liquid, and length, would vary depending on what different people could tolerate. Treatment frequency (daily vs 1x/week), and varying lengths could also be tested at this point. Possibly test with/without inducing diarrhea beforehand to clear out the intestines. If someone is insistent on oral capsules only, then a bile acid sequestrant should be tested along side it. For me, taking a bile acid sequestrant with oral FMT seemed to increase effectiveness (but not resistance to perturbation). But I think you can get the same or better results by using both upper and lower routes.

    3. If we're still not getting ideal results then we can test mechanical clearance of the mucosa since using antibiotics is not supported. It would also be interesting to see how results differ if you use a whole stool vs filtering everything out other than the phages. I think that many cases of gut dysbiosis may largely be due to missing phages resulting in uncontrolled bacterial growth. So if you're adding both phage & bacteria, half of what you're adding may be unwanted.

    4. If we're still not getting ideal results, hopefully someone would have tested a mucosal microbiota transplant in an animal model, and if that is a more effective way of transplanting the mucus microbiota then we can try that in humans.

If after step one a superdonor is identified/confirmed, then do literally every test under the sun to see what sets them apart from other donors, so that our ability to identify donor efficacy & safety based on testing is drastically improved. Metabolomics, proteomics, phages, fungi, archaea, immune system components, 16s, shotgun, etc..

I'm not sure where placebo-control comes in. I've been waiting 4+ years to get FMT from a high quality donor. I've been close to death so many times due to lack of a high quality donor. There are other people who died due to the lack of a high quality donor. Is it ethical to give us placebo? If I got placebo I could be waiting another 4 years for another opportunity.

EDIT: The way the ASU autism team is doing placebo in 2019 seems like a good way to do it. The placebo group will get FMT after a number of weeks.
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My thoughts on transferring unknowns, or susceptibility/probability of later disease development:

The key is to find FMT donors with eubiotic, disease resistant, unperturbed, curative gut microbiomes. You can find these people, and reduce the risk of transferring susceptibility/probability of later disease development via the use of an extensive questionnaire that covers the donor's entire life, family, and family history. Eg: https://humanmicrobiome.info/fmt-questionnaire/

Even though the example given in that link (Myron Rolle) is probably not the perfect donor (it looks like he's balding, which is immune system dysfunction I think), he's still a major improvement for >99% of the population. An acceptable risk:reward ratio can be achieved with sufficient donor quality. But also, he may have picked up a pathogen that triggered the immune system which resulted in balding. So at his current age he would be a lower quality donor, but if you got him at a younger age he wouldn't necessarily transfer balding-potential to an FMT recipient. The same goes for other diseases of old age. The diseases develop as the body deteriorates and pathogens accumulate. So if you can prevent that deterioration (prevent/cure dysbiosis and the resulting immune system dysfunction, via FMT from young healthy donors https://humanmicrobiome.info/aging/) then the disease won't develop, even if it's heritable.

My efforts to try and get this FMT trial done:

Besides emailing the 180 or so researchers doing FMT clinical trials, I also:

Looked through the recent published research on IBS and CFS and wrote to American authors on those papers asking them if they were able to do an FMT clinical trial with high quality donors, or if they had a recommendation for who to contact. I also looked up major microbiome research centers in the US and wrote to them. There are quite a few in my Southern California area. But again they didn't seem interested.

Someone advised me to write to American gastroenterology association authors on IBS guidelines, and US authors on the Rome Foundation IBS guidelines, and same for the CFS researchers. So I did write to dozens of those people but none were able & willing to do an FMT clinical trial.

This microbiome webinar I just watched had a great comment from Dr Amy Proal about how lack of access to clinical trials also means they are losing useful data due to people having to resort to DIY.

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You can use the microbiome forum for discussion. The Blogger commenting system is pretty bad.

Previously posted on /r/fecaltransplant.

See previous posts about FMT donor quality under the "FMT" section here: https://maximiliankohler.blogspot.com/p/blog-page.html