The Super-Donor Phenomenon in Fecal Microbiota Transplantation (Jan 2019, review) FMT

[Michael Harrop]

https://www.frontiersin.org/articles/10.3389/fcimb.2019.00002/full

An important paper to have submitted here.

Fecal microbiota transplantation (FMT) has become a highly effective bacteriotherapy for recurrent Clostridium difficile infection. Meanwhile the efficacy of FMT for treating chronic diseases associated with microbial dysbiosis has so far been modest with a much higher variability in patient response.

Notably, a number of studies suggest that FMT success is dependent on the microbial diversity and composition of the stool donor, leading to the proposition of the existence of FMT super-donors.

The identification and subsequent characterization of super-donor gut microbiomes will inevitably advance our understanding of the microbial component of chronic diseases and allow for more targeted bacteriotherapy approaches in the future.

Here, we review the evidence for super-donors in FMT and explore the concept of keystone species as predictors of FMT success. Possible effects of host-genetics and diet on FMT engraftment and maintenance are also considered. Finally, we discuss the potential long-term applicability of FMT for chronic disease and highlight how super-donors could provide the basis for dysbiosis-matched FMTs.

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Unfortunately, the authors of this review didn't bother to attempt to find a super-donor for their FMT trial: https://forum.humanmicrobiome.info/threads/effects-of-fecal-microbiome-transfer-in-adolescents-with-obesity-the-g.474/

 

[Michael Harrop]

Comment from a previous thread:

Another user mentioned that this should be common sense, which I agree with, and have been surprised at the amount of people arguing against it. Personally I would think it would also be common sense for the universities doing FMT studies and other microbiome studies to turn to their athletics departments for donor recruitment.

I'm not sure if there are problems there or why it hasn't been done so far, but college athletes are probably one of the best groups of people to recruit donors from.

Despite the multi-donor and intensive dosing approach, Paramsothy et al. achieved post-FMT remission rates (FMT, 27% vs. placebo, 8%, p = 0.02) that were similar to those reported previously

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This is inline with what I said/discovered before: You cannot combine multiple low quality donors to create one high quality donor. Low quality donors all seem to be missing the same thing(s).

 

[SFBayFMT5]

They also say this though:

"Microbial dysbiosis is a blanket term for an unhealthy or imbalanced gut community. As such, the population structure that is considered to represent microbial dysbiosis is variable between different disorders (Duvallet et al., 2017). Moreover, the microbiome deficit of one individual may not necessarily mirror that of another individual and therefore it is not surprising that patients respond differently to FMT. As more FMT-related clinical and microbial data are generated, it is becoming clear that “one stool does not fit all” in the context of treating chronic diseases with microbial dysbiosis."

 

[Michael Harrop]

Moreover, the microbiome deficit of one individual may not necessarily mirror that of another individual and therefore it is not surprising that patients respond differently to FMT. As more FMT-related clinical and microbial data are generated, it is becoming clear that “one stool does not fit all” in the context of treating chronic diseases with microbial dysbiosis.

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Of course. But a likely reason is that they're all using low-quality donors, so of course there's more heterogeneity.

The wiki covers this: https://humanmicrobiome.info/fmt/#screening

There is a large amount of evidence (in this wiki) that donor quality (rather than compatibility) is the #1 factor. But of course each donor (and recipient) is very unique and thus some donors would have certain microbes needed to treat certain conditions/individuals, while others do not. And naturally there would be varying results when transplanting one unique microbiome into another. I compared it here to a jigsaw puzzle.

For donor quality, you'd be looking for a donor with the complete puzzle.

For donor matching you'd need to figure out which pieces the recipient is missing, and which the donor has and is able to transfer to the recipient.

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