Faecal transplants reverse hallmarks of ageing
uea.ac.uk
uea.ac.uk
1) A critical experiment to determine that it is bacteria (or fungal/virus) per se and not a host effector would be the transfer of contents from aged germ-free control mice (mice without microbes of any type). The authors mention a transfer protocol that could be optimized for fungal commensals, but don't address the more important germ-free control.
2) It is hard to characterize individual immune metabolites/signals (e.g. IL-10, IL-6, etc.) as either good or bad. The context determines the effect and they show changes in at least 20 cytokines in Fig 3E. While they focus on IL-6 and TNF, it's not immediately clear those are necessarily a part of pathogenic inflammageing. LBP conversely, seems pretty hard to interpret as anything but evidence of barrier permeability and this result seems strong.
3) It's not clear how much of this effect would sustain over the long term. The amount of time between fecal transplant and mouse sacrifice/result generation was only 18 days. Experiments with such a short duration seem like they might capture an unrelated effect due to some other coincident factor.
Overall, a well done paper with a lot of interesting things, but also reasons to be very skeptical of the magnitude of this effect. As usual, I will end with: you can dramatically improve your microbiome health (whatever that term actually means) by eating a high fiber diet like most humans did for most of evolutionary time.
Is that (primarily) because high fiber food takes so long to digest that it gives more time for "stuff" to propagate in your gut?
Fixing microflora (and hence influencing metagenome) however, is not that simple. You wont feed good bacteria only, but pathogenic too if you have them overpopulated, which will make things worst. You can't easily replace those with new ones coming from food because of the acid barrier. You might think that lowering it down is good idea, but its totally not, because you will soon find new neighbor h. pylory which can cause all kinds of shit, along with having less nutrientes available by stealing and unoptimal pH environment. Regular probiotics are usually meaningless (influencing environment like fart in the wind).
Eating carnivoir diet makes your acid stronger which further strenghtens your defences (only great if you don't have invaders).
Then, this is dynamic - good guys can become bad in specific context.
The best way to improve your microbiome health is to find FT surogate, some great probiotic like Visbiome or VSL3, eat fermented foods, use prebiotics, and obviously dont use antibiotics in relaxed manner (save them for emergencies, like once in decade, and even then help flora repopulation and good luck with fungi proliferation) and do not remove your apendix just for the sake of it.
Funny thing nobody mentiond antibiotics and how harmful they are. Yes, they can save your life but poping them every now and then borders to malpractice.
I am a software architect, not a doctor, but machine is a machine.
- https://pubmed.ncbi.nlm.nih.gov/35027429/
- https://pubmed.ncbi.nlm.nih.gov/35243408/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879739/
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000835/
- https://pubmed.ncbi.nlm.nih.gov/33676528/
Note, some of these are studies of humans and some are on mice
And I’m pretty sure one of the human studies does establish causation, although I don’t have time to see which one
Still, I hope that my post was received by the poster as informational, despite its somewhat harsh tone. No matter your background, knowing how to present your ideas in a non-confrontational way will surely make more people listen to you.
Let me guess you’re going to move the goalpost.
From a doctors perspective prescribing antibiotics encourages people to show up with minor illness, it’s bad medicine but good business practice.
Another study [1] I just found showed that older women who had been exposed to antibiotics for => 2 months had increased risk of all-cause mortality and cardiovascular mortality (hazard ratio 1.49). Interestingly, if they had also been exposed to antibiotics in middle-adulthood, their mortality rate was even higher; which may suggest that antibiotic exposure permanently impairs the microbiome. Paper's conclusion: "Long-term use of antibiotics in late adulthood may be a risk factor for all-cause and cardiovascular mortality. The unfavorable effect of antibiotic exposure for subsequent risks of deaths due to chronic diseases needs to be considered."
It's almost trite to say it at this point but correlation is not causation.
That seems like a very obvious case of correlation vs causation (people who need medicine are more likely to die than those who dont)
Please, this should be primary school knowledge nowadays.
This should have been one of the mandatory COVID prevention methods.
Uh huh
> some great probiotic like Visbiome or VSL3
Sure are a lot of "you watered down the product" and false advertising lawsuits against these guys.
Can supplementation be an effective substitute for fiber derived from real foods? If so, are there any particular kinds of supplements you'd recommend?
Whatever psyllium you choose, be careful of lead content. https://www.consumerlab.com/reviews/psyllium-supplements/psy... has reviews and analysis of 8 products, including lead content.
I’ve been using this stuff almost daily for many years.
“ALA, the most common omega-3 fat, is an essential fatty acid that is converted into EPA and DHA. However, this conversion process is inefficient in humans. On average, only 1–10% of ALA is converted into EPA and 0.5–5% into DHA”
It would be like trying different gasoline additives instead of taking your car to the car wash.
CTO of Microsoft wrote 6 books on molecular gastronomy named Modernist Cousine [1]. There are lots of pages in first book about managing environmental fecal matter (hint: there is a LOT of it around you and in the food you eat).
Another idea I’m curious about would be to preserve fecal samples from a young mouse and transplant back to their older selves to see if that also shows the same effect.
Along these lines, are there any potential health benefits to penis in butt sex? Or does the poop need to enter my butt?
People born with C-section before this was known have higher rates of various digestive diseases. At leading hospitals, faecal transplants are done to c-section babies.
Natural birth is messy. Infants get covered in all sorts of slime, some of which occurs at "first light", right outside the body.
That bears repeating. One of the grossest things I've ever witnessed (which wasn't something dead) was my son immediately after he was born. I was impressed.
The bacterial transfer happens after the placenta has broken and the baby is being pushed out of the vagina. The vaginal opening and anus are inches away. The woman is bearing down to push out the baby and there can be discharges from the anus. Even if that doesn't happen, the area around the anus isn't entirely antiseptic.
Fecal transplants do not happen during birth. How would that occur?
However, it is commonly believed that vaginal fluid getting in the mouth of the infant is a mechanism for passing down flora between mother and child.
Would you believe that babies can get more than vaginal fluids in their mouths?
EDIT: Pedantically, I know that's not a 'transplant,' but I think GP was trying to 'not be gross.'
On the contrary, I think that would generally be considered a fecal transplant. I believe the history of the procedure started with oral administration of the transplanted material, mixed into a chocolate milkshake.
Many women never get back to the shape they were in before birth and stay fat after? Could be a permanent change in their gut bacteria, caused by the baby to get the mother to overeat to produce more milk for the baby.
https://my.clevelandclinic.org/health/treatments/22096-vagin...
A wise statement!
We obviously advised against this practice since there are a lot of unknowns, but what moms do with their babies in their room is up to them.
breathing intensifies
screams in Miamian
https://www.thisamericanlife.org/484/doppelgangers
Apparently it tastes slightly off calimari.
I would assume it's washed of fecal matter, and frying kills anything still living on the surface.
Keep in mind that sausage it traditionally made with the linings of pig intestines. So...
There is a reason why households have similar microbiome a over time - despite good hygiene practices bacteria (even fecal bacteria) will be passed from person to person.
There is zero need to do a fecal transplant on a baby that is delivered via c-section, except in some rare case where they get a C. difficile infection or something.
I'm guessing the next step here is to try this in humans. Would there be less regulations/approval times involved in doing this vs say testing a new anti-ageing drug?
I think you're reading way too much into it, poop is practically food.
There is also evidence that fecal transplant recipients take on physical and mental traits of the donor.
Quoting from https://www.abc.net.au/news/2017-05-09/faecal-transplant-sid....
"There have been people who have taken on the shape of the donor, such as if the donor is either overweight or underweight they've become more like that."
"There's even been reports of some people who have never been depressed getting a transplant from someone who's had depression and ending up with their first episode of depression after that."
Step two pretend to be a 6'6" Olympian fit to leave 100 years and die a barely aged god with great hair in Indiana Jonesque adventure.
Step three omitted for grossness.
Step four profit!
But yeah, reading the stories like what you linked is why I am very wary - I really want to be able to get a prepared mix of isolated, cultured, known good bacteria that can be inserted in to just seed some more of the good stuff. I think that removes a lot more of the ‘ick’ factor (even if the bacteria strains were originally isolated from faecal samples) even though what I have is bad enough that I would totally do a normal FMT if I thought it was safe enough!
Then again, it seems like in general the biggest gut bacteria problems come from an overpopulation of one type and not enough diversity which intervention seems less likely to cause.
There are also parasites which could be transferred but I really doubt that this would happen accidentally (hookworms, tapeworms, other things I don't know about).
But this is always a good thought.
If some treatment has the capability to actually help, it also has the capability to harm, there really isn't such thing as something which is exclusively good regardless of how you use it.
Reminds me, it's probably time to source some more kefir grains!
Not sure how well tracked it is for less-official/more DIY attempts.
Lots of others have had positive effects, but there's definitely some risk involved.
Then I heard about this probiotic bacteria called limosilactobacillus reuteri which was implicated in a bunch of studies as something that they used to find in people's guts back before processed food really became a huge thing and all these very clear links to a variety health effects (I'll just link the wiki page) [1]. When I went to the store it was the most expensive on the shelf, 40$, but I figured why not and got a couple of them. Haven't had any gut issues since.
I think there's worse things you can do to your guts than using the right probiotics for sure.
I think they identified compounds this bacteria makes that kills off and outcompetes others which may be causing you problems basically
In my case, I had debilitating health issues after a round of food poisoning that nearly took my life. In my specific case, the FMT's have helped a lot. Certainly, it is not without risks; however, one can minimize their risks by testing donor's stool, and asking for a full mental and physical evaluation to be performed.
Needless to say, I was unpleasantly surprised when I clicked the link.
whereas Enterorhabdus caecimuris, Turicimonas muris, and Muribaculaecae bacterium DSM 103720 were significantly enriched in the young vs. old group
https://www.smithsonianmag.com/arts-culture/franken-berry-th...
Sounds like a great topic for Silicon Valley fanfic:
For example, I have a family member with Crohn's and the majority of doctors they saw were adamant that diet would not alter the symptoms of the disease, and the only way to treat it was using drugs like prednisone (steroid) or Humira (TNF blocker), both of which can have awful side effects.
With some major dietary adjustments, and the guidance of "non-traditional" doctors, my family member is in full remission, and has met countless other people with Crohn's, Hashimoto's, and other diseases caused by chronic inflammation who have essentially been cured this way, too.
The science/theory may have changed, but the potential link between gut microbiome and autism for awhile was thought to do with the levels of Clostrium (Clostridia?... can't remember back to my microbiology days) bacteria in babies. Most babies are born with high levels of Clostridium species in their gut, as you may know, clostridium are usually very good at producing toxins (botulism, c. diff, perfringens etc). Majority of babies seem to get rid of these bacteria at 10 months or so, but those with autism seem to hold onto them. The thinking is these bacteria continue to produce low levels of neurotoxins that affect the brain. It seems to be supported with anecdotal research which shows improvement in autism symptoms in younger children who are given transplants but not older children. The thought being the years of toxin affect on the brain has been too much.
Diabetes: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415231/
Even cancer cells: https://www.frontiersin.org/articles/10.3389/fimmu.2021.6220...
The NIH Human Microbiome project: http://commonfund.nih.gov/hmp
"recipients were ... twice delivered ... donor microbiota ... by oral gavage of fecal slurry preparation."
More seriously the linked article didn't mention that for the recipients they destroy the existing microbiota via multiple antibiotics prior to transplant of the new.
Not everything that works in a mouse model works in humans.
Apparently, it was a thing!
It works with severed body parts though.
This is what you would expect from freezing. It preserves things. The difficulty with freezing is getting back up to normal temperatures safely. (And the creation of ice crystals, which can be very damaging.)
https://en.wikipedia.org/wiki/Emergency_Preservation_and_Res...:
Emergency Preservation and Resuscitation (EPR) is an experimental medical procedure where an emergency department patient is cooled into suspended animation for an hour to prevent incipient death from ischemia, such as the blood loss following a shooting or stabbing.
That page doesn’t say this is a net win or worked well at all, but it’s a difficult line of research. Not only are the first patients almost dead at the start of the process (as is always the case with high-risk of death experimental procedures), but there also is no way to know when a patient will show up.
https://en.wikipedia.org/wiki/Deep_hypothermic_circulatory_a... is easier in this respect:
Deep hypothermic circulatory arrest (DHCA) is a surgical technique that induces deep medical hypothermia. It involves cooling the body to temperatures between 20 °C (68 °F) to 25 °C (77 °F), and stopping blood circulation and brain function for up to one hour.
I think that’s a proven winner for some patients, but only at relatively high temperatures (“Profound hypothermia (< 14 °C) usually isn't used clinically. It is a subject of research in animals and human clinical trials”)
When you consider that oxygen deprivation is the primary cause of cell death it makes sense. Cooling down the cells greatly reduces their metabolism and thus oxygen requirements. But cooling the heart down before the brain just makes the brain run out of oxygen first. The more oxygen-dependent the organ the more critical it is that organ be cooled first. Conversely you can't warm up those organs before the heart and lungs or they'll survive that long time of cooling only to die during warming due to lack of oxygen.
Edit to add an interesting related video: https://www.youtube.com/watch?v=2tdiKTSdE9Y
Don't think a 21st century ethics board is gonna be onboard for doing such an experiment either.
What must be said though is that while freezing allow for partial body rescuscitation, let's not be fooled. The mice or body part might behave normally, but the body has suffered from a lot of possibly permanent damage (conformational changes, oxidative stress). I expect rescuscitated humans to have a lower quality of life and reduced lifespan, although that's fucking worth it for being rescuscitated!! One reason is that ice has that annoying property of taking more volume than water. This has consequences. However modern cryogenics aims to vitrify water, which is a special kind of ice that does not take more space! What people don't know is that structurally preserving organs AKA cryogenics, is a solved problem. Researchers have done that sucessfully to a pig's brain, preserving 100% of its structure. The current issue is that while we can preserve the body without structural losses, we don't know how to reanimate it because the chemicals they uses become toxic upon reanimation and there is no known way to extract it fast enough. As a reminder, before rescuscitating humans, cryogenics will allow better preservation of blood and organ donations.
https://news.ycombinator.com/item?id=31144130
("The Woman Who Survived the Lowest Body Temperature Ever")
Search my comment history for a deeper dive on this one. It's not a productive reply. You might not like it, but that is the state of the art. Animal models are 100% a valid way to do things.
Also ITT: HN figures out that natural childbirth involves poop touching a newborn. Cmon, seriously? How do you not know this?
Even if I hate this idea, just for the sake of argument: What about animal models closer to humans?
Rodents are not primates:
* Phylogeny tells they are very far from primates:
https://en.wikipedia.org/wiki/Glires
* In some rodent species, the tail is capable of regeneration.
* It can refresh them.
* Rodents have efficient digestive systems, absorbing nearly 80% of ingested energy.
* They can eat cellulose. They have specific bacteria in their guts that can reduce it to its carbohydrate elements.
* Some species are sensitive to ultraviolet light.
* Whisker action is mostly driven by the brain stem, which is itself provoked by the cortex
I strongly agree with you that primates would be a better model, from a cost is no object, no public opinion perspective. In fact, probably to many people's non-surprise, most primate work has been moved to China to avoid scrutiny. Last I saw at my place, primates were primarily (ha!) used for behavioral studies and nothing grisly.
I'll see your "here are the differences" and raise you a here are the similarities to humans:
* We're around 85% genetically identical to mice overall if we dump (actually controversial idea) junk DNA. This number varies on who you ask.
* Certain genes can be up to 99% the same. Your gene of interest being similar is important.
* We're both mammals. (some models are not)
* We share many of the same biochemical systems, endocrine, etc.
* Many genes for known diseases are shared. Disease similarity can be very high. (think cancer, atherosclerosis, diabetes)
* Mice can be made immunodeficient and used with human material.
* Very well studied life cycle, and measurement of health. We know most measurable parameters and their nominal ranges.
To harmonize with your idea of differences to humans here are the ones that make mice even more useful:
* Reproduce fast, this means ideas can be tested early and often.
* Small. Cheap to house, and make at scale.
* Genetically identical clones: we're better than ever at this now. This increases our ability to repeat and vet research.
It is completely standard for work to be done in mice. This constant dismissal of mouse models is a nothing burger. Animal models don't always pan out, however that's the state of the art.
I agree with you that in a no holds barred world primates would be universally better. In the US, IACUC exists because of primate experiments gone off the rails at Penn in the 80s. "Unnecessary Fuss" is the vid/incident. Video release was 83 I think? IACUC showed up 1985. This put primate work in the US under intense scrutiny and not without reason.
Oh and for what it's worth, I've never see a lab rodent's tail come back in 6 years of working with them. :) You are sending me on a new search!
Maybe if we're lucky we'll see a response from microbiome person.
I'll admit my reply was spicy, but grandparent's reply is borderline noise / bot tier discourse. HN can do better, and I think your reply is a good sign of that!
This’ll prob get downvoted but I couldn’t resist.
https://www.dailymail.co.uk/video/femail/video-2323636/Video...
Seeing the wealthy glitterati pay $$$ top dollar for literal sht (refined or not), and then pay to it have shoved up their ss.
I am certain mavrick doctors in LA will start experimental treatments shortly for those who wish to stay young and are willing to pay.
A non-profit I believe, but it is a company collecting and distributing fecal material for transplants.
Poopr (YC S23): Platform for hacking your gut bacteria, written in Rust
/s
The thing is 1) people, including most researchers, are scientifically illiterate 2) In addition to mediocrity, incentives are fundamentaly extremely broken given that those peptides, being endogenously produced by the human body (a trenscendant characteristic versus synthethic drugs, which dramatically reduce the propensity of side effects)) it is not patentable. Substances endogenously created by the body cannot be patented and therefore cannot be monetized hence nobody will ever pay clinical trials. Of course a world where medecine can't leverage the same tech as the human body is doomed to be very limited.
If you wanna add some substance to the discussion, learn the topic: https://pubmed.ncbi.nlm.nih.gov/?term=bpc+157&sort=date
Are you familiar with Miracle Mineral Supplement?
> 1) people, including most researchers, are scientifically illiterate
Wouldn't you need to be an expert in this field to know?
All that coming from the folks which supposedly like to hack around, while this machine called body is taken by totally different standards. I see next to 0 curiosity, exploration, auditing, logging, do-it-yourself attitude. Stakes are higher, eh ?
Or did I imagine sentences like FT works only in mice, are there downside of messing with gut bacteria? (omg?), do people really eat shit (wtf?), how poop transfers during birth (:S) ...
Amazing. Bring it on now!