Michael Harrop
Active member
I posted about this a few years ago elsewhere [1][2][3] and I'm copying all the info here for easy discussion.
"While fecal microbiota is partially normalized by extended co-housing, mucosal communities associated with the proximal colon and terminal ileum remain stable and distinct". Comparison of Co-housing and Littermate Methods for Microbiota Standardization in Mouse Models (May 2019). https://www.cell.com/cell-reports/fulltext/S2211-1247(19)30488-7
For the people who don't know, mice eat each other's poop, thus naturally do FMT when co-housed.
This study seems to show that FMT is not enough to change the mucosal microbiome. Thus it seems like something like this would be necessary to enhance FMT:
Previously I emailed a bunch of IBS & CFS researchers asking them to test that mucosal clearing either by itself or in conjunction with FMT, but it didn't seem like any were willing/able.
Someone should also test (in vitro then in mouse models) various substances that degrade/clear the gut mucosa to see if you can find one that safely boosts the ability of FMT to replace the mucus microbiota. Basically a chemical version of the method above. N-acetyl cysteine (NAC) might be one. Try while liquid fasting too.
Someone suggested:
And relevant to the "in vitro" part: GuMI: New In Vitro Platforms to Parse the Human Gut Epithelial-Microbiome-Immune Axis https://grantome.com/grant/NIH/R01-EB021908-02
My worry is that the fecal microbiome isn't adequate, and a gut microbiome transfer will require harvesting the mucosal microbiome. But an experiment like this should help to further our understanding of this.
I'm thinking there might be some type of layers. Like the microbes transferred by FMT are only able to occupy some top layer or small niches where they're able to feed on the food coming through, but unable to penetrate further down into the mucus.
This is very much inline with my own current FMT experience where the donor microbes seem to be very easily lost - such as by using iodized salt (iodine is an antimicrobial) - and I have to keep adding them.
It should be possible to do a mucosal microbiota transplant by swabbing/collecting mucosa samples from the colon, immediately submerging them in saline to protect anaerobes, and then feeding that liquid to other mice and see how it compares to FMT/co-housing. I would also compare feeding the mucosa liquid while the recipient mouse was fasting vs not fasting.
I did a google scholar search for "mucus microbiota transplant" and didn't see anything on it.
We could even do it in humans, it would just be slightly more invasive for the donor than FMT. I've had a colonoscopy done while I was not sedated. It was painful as the object made its way through the turns especially, but perhaps we don't need to use such a large object, making it less painful.
For reference, the mucosal microbiota seems to be significantly different from the fecal microbiota:
Maybe the ultimate end game will be clearing the mucosa in the recipient and using mucosa microbiota from the donor, but for now, maybe whichever one is easier could be a significant improvement on its own compared to standard FMT.
"While fecal microbiota is partially normalized by extended co-housing, mucosal communities associated with the proximal colon and terminal ileum remain stable and distinct". Comparison of Co-housing and Littermate Methods for Microbiota Standardization in Mouse Models (May 2019). https://www.cell.com/cell-reports/fulltext/S2211-1247(19)30488-7
For the people who don't know, mice eat each other's poop, thus naturally do FMT when co-housed.
This study seems to show that FMT is not enough to change the mucosal microbiome. Thus it seems like something like this would be necessary to enhance FMT:
Previously I emailed a bunch of IBS & CFS researchers asking them to test that mucosal clearing either by itself or in conjunction with FMT, but it didn't seem like any were willing/able.
Someone should also test (in vitro then in mouse models) various substances that degrade/clear the gut mucosa to see if you can find one that safely boosts the ability of FMT to replace the mucus microbiota. Basically a chemical version of the method above. N-acetyl cysteine (NAC) might be one. Try while liquid fasting too.
Someone suggested:
And relevant to the "in vitro" part: GuMI: New In Vitro Platforms to Parse the Human Gut Epithelial-Microbiome-Immune Axis https://grantome.com/grant/NIH/R01-EB021908-02
My worry is that the fecal microbiome isn't adequate, and a gut microbiome transfer will require harvesting the mucosal microbiome. But an experiment like this should help to further our understanding of this.
I'm thinking there might be some type of layers. Like the microbes transferred by FMT are only able to occupy some top layer or small niches where they're able to feed on the food coming through, but unable to penetrate further down into the mucus.
This is very much inline with my own current FMT experience where the donor microbes seem to be very easily lost - such as by using iodized salt (iodine is an antimicrobial) - and I have to keep adding them.
Mucosal microbiota transplant?
I was thinking more about "while fecal microbiota is partially normalized by extended co-housing, mucosal communities associated with the proximal colon and terminal ileum remain stable and distinct".It should be possible to do a mucosal microbiota transplant by swabbing/collecting mucosa samples from the colon, immediately submerging them in saline to protect anaerobes, and then feeding that liquid to other mice and see how it compares to FMT/co-housing. I would also compare feeding the mucosa liquid while the recipient mouse was fasting vs not fasting.
I did a google scholar search for "mucus microbiota transplant" and didn't see anything on it.
We could even do it in humans, it would just be slightly more invasive for the donor than FMT. I've had a colonoscopy done while I was not sedated. It was painful as the object made its way through the turns especially, but perhaps we don't need to use such a large object, making it less painful.
For reference, the mucosal microbiota seems to be significantly different from the fecal microbiota:
Maybe the ultimate end game will be clearing the mucosa in the recipient and using mucosa microbiota from the donor, but for now, maybe whichever one is easier could be a significant improvement on its own compared to standard FMT.
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