What are the specific microbes found, and also those that should not be found in the stool of a superdonor? Perhaps just culturing these microbes separately is sufficient to make a good insertible pill?
There are companies trying to identify that, and use it to create “synthetic” FMT capsules, but it’s largely not yet known, and in my opinion it will be decades before we can replace whole stool with synthetic FMT.
My gut feeling (no pun intended) says the mythical “super-donor” is a very good excuse to keep looking / trying without having to present better results, and may never be found. Doing the search directly in the “microbiome composition space” instead of doing it on people (thereby indirectly sampling the space) feels way more efficient, assuming it is tractable at all.
If some people are already looking into synthesis, is there anything happening in the direction of “extrapolating” towards better samples? (I.e. take several good-but-not-great donors that fall short in different ways, look at what’s same / different between their microbiome, then experiment with compositions that ought to be better according the current understanding, and repeat.)
I think your comment ignores the plethora of evidence supporting donor-quality hypotheses. Much of it was presented in the OP, and covered the permanent extinction of our host-native microbiomes, along with the exponential rise in chronic disease.
Your suggestion seems to be to “try to find a plethora of plant and wildlife species in a forest that has been burned to the ground”. Whether you can piece it back together is unknown, but I don’t think that’s the best approach to take right now.
Also, one of the major problems is that most people are not even bothering to look for high quality donors, and expecting FMT to get great results with low quality donors. The gut microbiome is incredibly complex, and we are so far from understanding it well enough [1] to be able to replace whole stool with synthetic FMT. Though I’m not discouraging people from trying it, and making headway there.
There is a tremendous amount of antibiotic overuse/abuse in the medical system. The current guidelines are likely far too generous in promoting their use, and there’s even 30%+ overuse according to current guidelines.
I had an extremely depressing related event recently. I had a donor applicant that was seemingly perfect in every way. Their physical condition and ability were amazing/perfect. Their mental condition seems fantastic as well. But someone gave them frequent amounts of antibiotics over their lifetime, which was almost certainly unnecessary. And now they’re suffering the consequences of it (in seemingly-subtle ways).
There are research groups that have largely given up on finding ideal microbiomes in modern society, and have thus resorted to visiting remote tribes, such as the Hadza [1][2].
I know from experience (unfortunately only temporary) that such “ideal donors” do exist in modern society. They’re just very rare, and it even seems that the people more likely to qualify are less likely to apply. Many of them are blissfully excelling in life and don’t need/want to be bothered by some “weird poop thing”. Many of them are making millions of dollars, or on their way to make millions of dollars and don’t want to jeopardize that opportunity.
There are research groups that have largely given up on finding ideal microbiomes in modern society, and have thus resorted to visiting remote tribes, such as the Hadza [1][2].
If I remember right Bruce Sterling wrote in 1998 in his sci-fi novel Distraction about how when a frozen body was found, there was an immediate commercial interest to sequence the gut microbiome. It’s interesting how our world evolves into that future ;)
My understanding is that as of now we know waaay too little about the gut microbiome to make this “direct search in microbiome composition” viable. For example, we basically have no clue about bacteriophages in the gut. Yet they probably play an important role in gut health, and in the efficacy of FMTs.
Also, even if we knew exactly what composition we wanted, we aren’t very good yet to “synthesize it”/grow it in the lab.
Sure, “the reason it doesn’t work better is because we need better donors” sounds like a nice excuse. But it is at least suggestive that this is indeed the case. The better the donor criteria, the better the study outcomes. If we extrapolate this to even higher criteria…
Btw. poor donors are not the only (avoidable!) reason FMTs often show poor results. See the post.
If you make an insertable pill with X predefined microbes, the FDA/EMA likely want you to get it approved as a drug.
HumanMicrobiome sounds like a project that’s doable with a million-dollar as capital. I expect that you might need a billion to do a proper job at the synthetic FMT capsule task.
I’m confused. Human Microbes is already being done with hardly any money?
Michael Harrop is basically a complete amateur, and he’s been doing it for a while now.
What do you mean with Human Microbiome. What project are you talking about?
Sure, the things you mention need FDA approval and are super expensive.
Of sorry, I got the name wrong. I wanted to say that the thing that Michael Harrop does is possible to do with little money because even the FDA seems to understand that it would be crazy to require clinical tests for approving individual donors.
On the other hand, if you would start a project for synthetic FMT capsules, I doubt that it could be done at that funding level in the current regulatory environment.
What are the specific microbes found, and also those that should not be found in the stool of a superdonor? Perhaps just culturing these microbes separately is sufficient to make a good insertible pill?
There are companies trying to identify that, and use it to create “synthetic” FMT capsules, but it’s largely not yet known, and in my opinion it will be decades before we can replace whole stool with synthetic FMT.
After all, you have to find a super-donor first.
My gut feeling (no pun intended) says the mythical “super-donor” is a very good excuse to keep looking / trying without having to present better results, and may never be found. Doing the search directly in the “microbiome composition space” instead of doing it on people (thereby indirectly sampling the space) feels way more efficient, assuming it is tractable at all.
If some people are already looking into synthesis, is there anything happening in the direction of “extrapolating” towards better samples? (I.e. take several good-but-not-great donors that fall short in different ways, look at what’s same / different between their microbiome, then experiment with compositions that ought to be better according the current understanding, and repeat.)
I think your comment ignores the plethora of evidence supporting donor-quality hypotheses. Much of it was presented in the OP, and covered the permanent extinction of our host-native microbiomes, along with the exponential rise in chronic disease.
Your suggestion seems to be to “try to find a plethora of plant and wildlife species in a forest that has been burned to the ground”. Whether you can piece it back together is unknown, but I don’t think that’s the best approach to take right now.
Also, one of the major problems is that most people are not even bothering to look for high quality donors, and expecting FMT to get great results with low quality donors. The gut microbiome is incredibly complex, and we are so far from understanding it well enough [1] to be able to replace whole stool with synthetic FMT. Though I’m not discouraging people from trying it, and making headway there.
I would recommend anything by Martin Blaser. I also have a wiki section here on the permanent damage from antibiotics, that extends even beyond their killing of microbes: http://humanmicrobiome.info/Intro#more-effects-of-antibiotics
There is a tremendous amount of antibiotic overuse/abuse in the medical system. The current guidelines are likely far too generous in promoting their use, and there’s even 30%+ overuse according to current guidelines.
I had an extremely depressing related event recently. I had a donor applicant that was seemingly perfect in every way. Their physical condition and ability were amazing/perfect. Their mental condition seems fantastic as well. But someone gave them frequent amounts of antibiotics over their lifetime, which was almost certainly unnecessary. And now they’re suffering the consequences of it (in seemingly-subtle ways).
There are research groups that have largely given up on finding ideal microbiomes in modern society, and have thus resorted to visiting remote tribes, such as the Hadza [1][2].
I know from experience (unfortunately only temporary) that such “ideal donors” do exist in modern society. They’re just very rare, and it even seems that the people more likely to qualify are less likely to apply. Many of them are blissfully excelling in life and don’t need/want to be bothered by some “weird poop thing”. Many of them are making millions of dollars, or on their way to make millions of dollars and don’t want to jeopardize that opportunity.
If I remember right Bruce Sterling wrote in 1998 in his sci-fi novel Distraction about how when a frozen body was found, there was an immediate commercial interest to sequence the gut microbiome. It’s interesting how our world evolves into that future ;)
My understanding is that as of now we know waaay too little about the gut microbiome to make this “direct search in microbiome composition” viable. For example, we basically have no clue about bacteriophages in the gut. Yet they probably play an important role in gut health, and in the efficacy of FMTs.
Also, even if we knew exactly what composition we wanted, we aren’t very good yet to “synthesize it”/grow it in the lab.
Sure, “the reason it doesn’t work better is because we need better donors” sounds like a nice excuse. But it is at least suggestive that this is indeed the case. The better the donor criteria, the better the study outcomes. If we extrapolate this to even higher criteria…
Btw. poor donors are not the only (avoidable!) reason FMTs often show poor results. See the post.
If you make an insertable pill with X predefined microbes, the FDA/EMA likely want you to get it approved as a drug.
HumanMicrobiome sounds like a project that’s doable with a million-dollar as capital. I expect that you might need a billion to do a proper job at the synthetic FMT capsule task.
I’m confused. Human Microbes is already being done with hardly any money? Michael Harrop is basically a complete amateur, and he’s been doing it for a while now.
What do you mean with Human Microbiome. What project are you talking about?
Sure, the things you mention need FDA approval and are super expensive.
Of sorry, I got the name wrong. I wanted to say that the thing that Michael Harrop does is possible to do with little money because even the FDA seems to understand that it would be crazy to require clinical tests for approving individual donors.
On the other hand, if you would start a project for synthetic FMT capsules, I doubt that it could be done at that funding level in the current regulatory environment.