Washed microbiota transplantation improves sleep quality in patients with sleep disorder by the gut-brain axis (Jun 2024, n=63) FMT 

Fecal Microbiota Transplants

Michael Harrop

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https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2024.1415167/full

Background: The clinical impact of washed microbiota transplantation (WMT) from healthy donors in sleep disorder (SD) patients is unclear. This study aimed to investigate the effect of WMT in SD patients.


Methods: The clinical data were collected from patients with different indications receiving 1–3 courses of WMT, divided into two groups by 7 points of PSQI scale. The score of PQSI and SF-36 scale was used to assess the improvement in sleep quality and life quality among patients with sleep disorders following WMT. Finally, 16S rRNA gene amplicon sequencing was performed on fecal samples of patients with sleep disorders before and after WMT.


Results: WMT significantly improved sleep quality in patients with sleep disorder in the short and medium term. WMT significantly improved sleep latency, sleep time and total score in the short term. WMT significantly improved sleep quality and total score in the medium term. In terms of sleep quality and sleep latency, the improvement value also increased with the increase of treatment course, and the improvement effect of multiple treatment course was better than that of single and double treatment course. In the total score, the improvement effect of double and multiple treatment was better than that of single treatment. WMT also improved quality of life in the sleep disorder group. WMT significantly improved general health, vitality, social function and mental health in the short term. WMT significantly improved role-physical, general health, vitality, and mental health in the medium term. WMT regulated the disturbed gut microbiota in patients with sleep disorders. In the normal sleep group, WMT had no effect on the decline of sleep quality in the short, medium and long term, and had an improving effect on the quality of life.


Conclusion: WMT could significantly improve sleep quality and life quality in patients with sleep disorders with no adverse events. The improvement in sleep quality resulting from WMT could lead to an overall enhancement in life quality. WMT could be a potentially effective treatment for patients with sleep disorders by regulating the gut microbiota.
 
Format correct?
  1. Yes
What would it take to implement something like this at HMorg? They used a sophisticated filtration device for the medical laboratory environment that is likely far too expensive for the average donor to acquire, but something similar to the filtration bags used by OpenBiome (https://pubmed.ncbi.nlm.nih.gov/33937092/, see section "Manufacturing") are available for use in making nut milks among other things.
 
1. There's no evidence that it's beneficial or necessary, so I wouldn't be interested.

2. If I were processing donor's stool in a central location it would turn me into a stool bank instead of a source of stool donors. Regulatory requirements would likely be drastically different. I would likely have to rent a laboratory and the costs for recipients would increase dramatically.

3. If "filtration bags" are available and affordable, recipients can request that the donor use one. They may need to purchase it similarly to how in the past when a recipient wanted the donor to use vacuum seal bags, they purchased the equipment for the donor.

4. Creating a mixture watery enough to easily filter may be another issue. The capsules we use would melt, and you also end up with a heavily diluted mixture.
 
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"1. There's no evidence that it's beneficial or necessary, so I wouldn't be interested."

In the companion paper where they define what a "washed FMT" is, they claim a significant reduction (almost a halving) in rate of adverse effects. That's the basis on which they chose to even do the washing for the study you directly linked--they wouldn't continue to do a work-intensive step if they didn't have data showing it seems to help.

The other points you make are valid. Though as for the last one, OpenBiome both filters and makes capsules. Maybe they use different capsules, but somehow they make it work.
 
Yeah, I shouldn't have used that wording. Thank you for correcting me. I have so much on my plate and mind, plus low brain function generally, all contributing to a bad statement like that :(

Washed microbiota transplantation (WMT) was similar to traditional FMT, but WMT has better safety, quality control, and effectiveness against diseases with flora disorders (Zhang et al., 2020).

Washed microbiota transplantation vs. manual fecal microbiota transplantation: clinical findings, animal studies and in vitro screening (Jan 2020) https://academic.oup.com/proteincell/article/11/4/251/6746748

Intraperitoneal injection in mice with the fecal microbiota supernatant obtained after repeated centrifugation plus suspension for three times induced less toxic reaction than that by the first centrifugation following the microfiltration. The toxic reactions that include death, the change in the level of peripheral white blood cells, and the proliferation of germinal center in secondary lymphoid follicles in spleen were noted.
Interesting that it was done in mice, thus you can't simply say "Well they used low-quality human donors".

However, their report of "toxic reactions that include death" seems to conflict with the vast majority of the FMT literature showing that FMT from healthy donors is safe. It also conflicts with case reports (including my own) indicating that "reactions from FMT" are often signs of an effective donor that "triggers the immune system and turns it back on".

The metagenomic next-generation sequencing (NGS) indicated the increasing types and amount of viruses could be washed out during the washing process.
So they are losing viruses in the process. That could be detrimental.

Metabolomics analysis indicated metabolites with pro-inflammatory effects in the fecal microbiota supernatant such as leukotriene B4, corticosterone, and prostaglandin G2 could be removed by repeated washing.
They are losing metabolites. I looked through to paper to confirm that there is no way to selectively decide what to remove or not remove. Merely, "we removed a bunch of stuff and the outcome was that there were fewer adverse events".

The followed washing process washed out a certain bacterial fragments, metabolites, soluble molecules, and proteins.
As noted above, the vast majority of FMT literature shows that FMT from healthy donors is safe, and thus there is no need to remove anything. I would be concerned that removing things likely results in lower efficacy, but they say it doesn't:
Importantly, the washed microbiota preparation did not affect the efficacy in both populations with UC and CD, compared with that by manual preparation for fecal microbiota (Wang et al., 2018; Ding et al., 2019).

In conclusion, this study for the first time provides evidence linking clinical findings and animal experiments to support that washed microbiota transplantation (WMT) is safer, more precise and more quality-controllable than the crude FMT by manual.

So there is support that WMT is safer than FMT, without a loss in efficacy. Personally, I'm not convinced that it's worth the trouble, or that there is definitely no loss in efficacy in all cases.

In my experience, "true" adverse events (not beneficial stimulation of the immune system, etc.) come from certain stool characteristics and donors. Can you take a "bad stool" and wash/filter it to make it safer? Probably. I still wouldn't recommend using that stool. It's better to discard it. But if you don't know how to identify bad stools, or if you don't have a donor who produces good stools, then you can probably get a safer result by washing/filtering it.

When it comes to AEs from donors, the main AE is their stool seemingly displacing or suppressing beneficial microbes from a previous donor. Is WMT going to prevent that? I highly doubt it.
 
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Yeah, I shouldn't have used that wording. Thank you for correcting me.



Washed microbiota transplantation vs. manual fecal microbiota transplantation: clinical findings, animal studies and in vitro screening (Jan 2020) https://academic.oup.com/proteincell/article/11/4/251/6746748


Interesting that it was done in mice, thus you can't simply say "Well they used low-quality human donors".

However, their report of "toxic reactions that include death" seems to conflict with the vast majority of the FMT literature showing that FMT from healthy donors is safe. It also conflicts with case reports (including my own) indicating that "reactions from FMT" are often signs of an effective donor that "triggers the immune system and turns it back on".
This is absolutely NOT MY personal experience. The FMT that had the most beneficial effects caused no temporary flaring of anything. In fact, this is my personal experience of medical treatments of ALL kinds--to the point where I've concluded that "die off reactions" are mostly a myth. The treatments that caused what seemed to be "die off reactions" ended up to be just sub-par treatments overall.

The toxic reactions that include death likely resulted from the intraperitoneal injection, which is not a particularly safe means of restoring the microbiome. In fact it's often how exaggerated negative responses or infections are provoked intentionally to then test treatments designed to ameliorate them.

So they are losing viruses in the process. That could be detrimental.
It COULD be, in theory, but they show no evidence it actually does.
They are losing metabolites. I looked through to paper to confirm that there is no way to selectively decide what to remove or not remove. Merely, "we removed a bunch of stuff and the outcome was that there were fewer adverse events".


As noted above, the vast majority of FMT literature shows that FMT from healthy donors is safe, and thus there is no need to remove anything. I would be concerned that removing things likely results in lower efficacy, but they say it doesn't:
The majority of the FMT literature (in humans) DOES seem to use some kind of purification step other than merely freezing stool and then administering it unaltered.


So there is support that WMT is safer than FMT, without a loss in efficacy. Personally, I'm not convinced that it's worth the trouble, or that there is definitely no loss in efficacy in all cases.

In my experience, "true" adverse events (not beneficial stimulation of the immune system, etc.) come from certain stool characteristics and donors. Can you take a "bad stool" and wash/filter it to make it safer? Probably. I still wouldn't recommend using that stool. It's better to discard it. But if you don't know how to identify bad stools, or if you don't have a donor who produces good stools, then you can probably get a safer result by washing/filtering it.

When it comes to AEs from donors, the main AE is their stool seemingly displacing or suppressing beneficial microbes from a previous donor. Is WMT going to prevent that? I highly doubt it.
 
From a related thread with more discussion:
Partial success with UT-AW-1998 for gut pain, food intolerances, and cognitive/mood symptoms (PANS-like)

I'm sure the clinics/providers who are doing this aren't just doing it to make more work for themselves
This is one reason for my initial poor statement of "there's no evidence for it". I have seen lots of "disgust" around FMT, from patients, researchers, and physicians. So up until now, it has largely seemed like it was being done due to disgust. There have even been efforts to rename "FMT" due to the disgust of "fecal".

From what I recall, the ASU autism team filtered the stool solely for the purpose of removing the taste and odor so that it could be drunk by the children. You could check their paper to verify.

The referenced paper is fairly recent (2020), and I had seen many instances of filtering occurring without a justified scientific reason. Clinics with low donor quality and other major deficiencies (including scientific) would cite some vague "we filter out the 'bad' stuff", without any proof that there is anything "bad" in stool. It seemed like they were doing it to make FMT more acceptable/less repugnant to their customers.

I still think there is likely nothing "bad" in high-quality stools.
 
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