Everyone's "poo-pooing" the article because the title doesn't mention mice, but, FWIW, stories of gut biota affecting humans behavior have been documented for a while.
Memory gain is noteworthy, which is the article's "wow" factor, but everyone's just knee-jerk smirking so ... here's a few random articles to gross you out about the wild world of trading microbiota and, for better or worse, changing your personality:
* "My butt made me crave candy."[1]
* "Gee, I'm not bipolar anymore thanks to my husband's butt juice infusion."[2]
The really crazy thing that happened to me when I changed diet to a more gut-biome friendly* is that (like I craved sweets before) I started craving vegetables and oatmeal. Like there was a regime change in my gut and the new guys pushed the buttons to get more of their food.
(less/no simple sugars, much more vegetables and starches/fibers, regularly eating 4 corn/20 plant oatmeal few times a week)
Fascinating to hear. I am trying to cut alcohol - still not entirely successful.
But I've been able to cut for months at a time. Whenever the cut happens, I feel my brain sort of "return" roughly a week or two in.
I'm not sure how to explain it other than something like fog clearing. Obviously makes some intuitive sense when you read it.
However, as someone that has consumed alcohol somewhat regularly (sometimes more, sometimes less) since college, it's bizarre to think about that consumption in retrospect. In effect, years and years of "fog" - it makes me wonder how different or similar life would have been without that fog.
Can't change the past now, but a data point and strong signal for the future.
weird. gal bladder removal made me a lot smarter too. no, really. cuz it didn't fix my problems either. well, it did but in an unexpected way. because it forced me to ask myself the real questions. so i started fixing my life, bit by bit. trial and error.
I think mainstream is mostly looking at the microbiome stuff wrong. Your microbiome is the downstream proxy of good lifestyle habits, not generally something to directly manage. Good diet, exercise, reducing stress, and sleeping well will improve digestion and all the downstream variables like microbiome, physical health, and mental health.
This is basic ecology, the bacterial population dynamics in your colon are a direct result of substrate availability. If it’s primarily fiber, polyphenols, and other indigestible plant compounds reaching the colon you’ll likely have a healthy microbiome. If instead you malabsorb food from poor lifestyle factors and have macronutrients reaching the colon they’ll probably fuel blooms of pathogens. I think microbiome researchers need to talk with ecologists more to help advance the field out of the myopia it’s in.
FMT does appear useful for special cases of infection like c-diff, but I think that’s led people to believe it’s a generally health promoting practice, when the research simply does not show it.
Replying to slibhb, while the research involving mental illness is not conclusive, fecal transplants are a known and accepted treatment for persistent C. diff (Clostridioides difficile) infection. Just for the record.
>The pattern with this stuff is that, when a blinded study is carried out, there's usually no effect.
It must be the case that these microbes need the subject to be aware of their presence! Maybe the microbes have consciousness, and for the treatment to work, the microbes' consciousness has to entangle (via quantum mechanisms) with the subject's consciousness? Blind studies prevent this quantum entanglement to form, that's why the treatment stops working. We definitely need more research in this direction!
They found a 15 point MADRS change in the placebo group, that's huge, it's only a 60 point scale, and more than the average SSRI produces. Either the procedure itself is doing something or something isn't right with the study.
Also one issue with all of these studies is they only look at averages and don't do subgroup analysis. It may be that a few patients have an underlying condition causing depression that is highly responsive to these interventions, while it has no effect on the others.
I would recommend the site https://gutbrainaxistherapeutics.com for learning more about Microbiota Transplant Therapy (MTT) and its opportunities, especially for Autism and Pitt-Hopkins Syndrome.
I’ll dig in more but my first question when I see this: who are the donors exactly? Like who decides what the ideal gut microbiome is and that John Doe is the guy to provide his fecal matter to the masses?
I would not recommend that site as a good resource.
Microbiome transplant therapy is a domain full of grifters right now who will push it to vulnerable populations desperate for hope, like parents of autistic children. The real research results are much less promising for difficult conditions.
Not only are there tons of papers, there are off-label treatments (some that have improved more than 80% of the folks I'm about to mention), and this isn't just about age related decline, but cognitive impairment in general. Long COVID, ME/CFS, TBIs, and other conditions are widely considered to have a similar origin. If you are interested in this stuff, I encourage you to look up all the scientific papers on this. It is fascinating stuff.
Serotonin produced in the gut doesn’t get into your brain.
This factoid is repeated everywhere but it’s misleading without knowing that gut serotonin is a different pool than brain serotonin and they have different functions.
The brain synthesizes its serotonin locally within the brain.
The blood brain barrier is a deny by default firewall. If there is no transporter configured for a particular molecule, it doesn't get through. There is no transporter for serotonin
This seems to be a recent anti-science meme to dismiss studies that use mouse models. I'm sure there is an interesting line of discussion about the strengths and limits of those models, but that's probably a complex, nuanced thread to pull, not something you blow off with a hand-waving internet comment.
To some degree the other posts are just pointing out the misleading "assumed protagonist" of the title (which doesn't mention mice) but I was surprised to see that the majority of posts boiled down to "eek! mice!"
I wish I could filter the word mice or mouse out of hn comments because as you say every single one are low effort gotcha's that I will never get my time back from.
It is like these armchair scientists don't understand that the actual scientists know the limits of the model system better than they do.
It's not anti-science, it's anti-science-journalism-hype.
Science depends on accurately reporting facts, being clear about the limits of your findings, and seeking explanations that survive scrutiny. Science journalism has other priorities that are often in conflict with those of science.
Yeah, it's a mouse study, but there are tons of human studies backing the whole gut-brain connection. There are even a bunch of books on it [1][2].
What's really cool is that the paper used low-dose capsaicin (just 5 μg/kg injected), and it completely restored hippocampal FOS activity and memory in older mice. Basically, that's the same stuff you get in cayenne pepper supplements - pretty easy to get your hands on.
I only have marginal knowledge about neuroscience, but one of my neuroscience professors in class would tell us
"You can cure anything in mice."
I don't know the mechanism why, but you can find tons of papers with incredibly strong results for curing of mitigating dementia, cognitive decline, addiction, etc in mice, but these almost never seen to work on people.
They're human specific ailments. We create a fake version of them in mice, then we fix the fake version. The basic problem with these issues is we don't understand the root cause. So we can replicate the symptoms in a mouse model then fix the symptoms, but that doesn't work in humans because the root cause is still there.
I guess it's because most major disorders and diseases have so many pathways at play that figuring out which one's actually causing the problem at the individual level is just too tricky.
The other thing concerns how potent the effect is to be therapeutic. In many cases, the effect is just marginal to be meaningful.
I've long regarded the great variety of chilis as its own distinct food group. But wonderful as they are for flavoring food, quite often in my home, I'm not sure how much of an effect orally consumed capsaicin has on memory functioning.
Conceivably parenteral capsaicin has different effects on hippocampal integrity or physiology than achievable with ingestion. I'm not familiar enough with disposition of capsaicin in the gut to comment further. My question is whether capsaicin passes from gut into the circulation in any appreciable quantity. I suspect it doesn't but I couldn't say I know for sure. I'll have to add it to the already long list of things I need to look up.
> What's really cool is that the paper used low-dose capsaicin (just 5 μg/kg injected), and it completely restored hippocampal FOS activity and memory in older mice.
There are countless papers published where simple ingredients produce miracles in mice. Most of them don’t replicate.
If you look up most food ingredients you can find someone, somewhere claiming to have used it to produce amazing outcomes in mice. After you read a lot of those you learn not to take individual papers seriously if the claims seem too good to be true.
IMO people should eat more fiber. A lot more fiber. It cleans the gut, the liver, absorbs cholesterol, slows insulin response and makes you feel full longer. The microbes in our guts need it to function.
Rather than jumping from one fad diet to another, just eat what you like and be sure to get a lot of fiber each day.
Agreed, but I think the mechanism relates to different microbes. If there are two microbes in your gut, and type A requires a dose of high-calorie, low-fiber food coming down the pipe every day, and type B is not able to reproduce as fast as type A but is able to live on high-fiber food, this tells you two things:
type A cannot have been living in humans thousands of years ago, but type B might have
type A benefits from making your brain worse at choosing healthy foods, and type B does not
Roughly what I follow. I pour chia seeds into everything I eat. Also: edamame, goji berries, green peas. Etc etc. My particular motivation is 1) health, but 2) I lift quite a bit and try to get as much protein from food as possible.
This has been the recommendation for general health for as long as I have been alive. Fiber is really important and there are plenty of easy healthy options that are cheap, unlike the astroturfed beef checkoff primal diet
I believe there is a lot of shame-induced ignorance around this whole subject. Culturally poopin' is in the similar category like sex or death, outlawed from most "civilized" debates. But consider how central digestion is to our existence: basically almost before everything else we must consume -> digest -> expel first. You are not getting that smart brain of yours without that poopy butthole to go along with it
"You" don't crave stuff, the microbiome in your intestine craves stuff.
There are microbes in there that specialize in eating, say, sugar. You don't give them sugar, they send signals to your brain saying "yo, more sugar"
This is why if you go on a sugar-free diet (just stop eating candy and sweets) the cravings just go away eventually. The microbes who keep shouting for more sugar either die away or go dormant.
True, I was kinda trying to allude that it's not the conscious you or your brain that craves things (usually), it's the gut/intestine flora sending the craving signals.
If this was true, sugar cravings would disappear when taking antibiotics that kill those microbes.
The fact that this doesn’t happen should give you pause about this woo-woo theory of cravings.
The reason you crave sugar and fat and other tasty things is that they taste good. You evolved in a world where feeling rewarded and driven to consume more of these was beneficial to survival when food was scarce.
Clearly "tasting good" is not the primary driver behind all of this. Good taste is an incentive to satisfy something more primary, similar like sex feels good in order to satisfy procreation
You’ve heard of The Selfish Gene theory from Richard Dawkins but I’ve started talking about The Sefish Tube. If you think about us another way, we are a tube of GI tract that does everything in its life and with its power to simply be full.
Readit News
Memory gain is noteworthy, which is the article's "wow" factor, but everyone's just knee-jerk smirking so ... here's a few random articles to gross you out about the wild world of trading microbiota and, for better or worse, changing your personality:
Crazy, right?1. I stopped drinking heavily and using other drugs, i.e. marijuana
2. managed my diet to avoid heartburn without medication
3. schedule my meals so it was easier to sleep at night (always eat something for breakfast when I wake up)
I did not need any "poo infusion" or anything.
I had a gal bladder removal that didn't fix the problems the doctors thought it would and got a lot smarter about the kinds and variety of food I eat.
I believe alcohol in particular was really screwing up my gut biome and entire digestive system.
Heavy alcohol use and marijuana are both known to impact memory and recall directly.
Discontinuing both of those explains changes in memory. Attributing this to microbiome changes does not follow.
For example
>I stopped drinking heavily and using other drugs, i.e. marijuana
Like the primary change you made was to cut out using a whole bunch of drugs with known, significant neurological effects.
(less/no simple sugars, much more vegetables and starches/fibers, regularly eating 4 corn/20 plant oatmeal few times a week)
But I've been able to cut for months at a time. Whenever the cut happens, I feel my brain sort of "return" roughly a week or two in.
I'm not sure how to explain it other than something like fog clearing. Obviously makes some intuitive sense when you read it.
However, as someone that has consumed alcohol somewhat regularly (sometimes more, sometimes less) since college, it's bizarre to think about that consumption in retrospect. In effect, years and years of "fog" - it makes me wonder how different or similar life would have been without that fog.
Can't change the past now, but a data point and strong signal for the future.
theorem of indirection, i guess.
Wow, it must be those gut microbes!
Here's a study that tried fecal transplants to treat mental illness (and found no effect): https://pubmed.ncbi.nlm.nih.gov/41785480/
The pattern with this stuff is that, when a blinded study is carried out, there's usually no effect.
https://pmc.ncbi.nlm.nih.gov/articles/PMC12536323/
It also found the effect was greater in people with IBS.
This is basic ecology, the bacterial population dynamics in your colon are a direct result of substrate availability. If it’s primarily fiber, polyphenols, and other indigestible plant compounds reaching the colon you’ll likely have a healthy microbiome. If instead you malabsorb food from poor lifestyle factors and have macronutrients reaching the colon they’ll probably fuel blooms of pathogens. I think microbiome researchers need to talk with ecologists more to help advance the field out of the myopia it’s in.
FMT does appear useful for special cases of infection like c-diff, but I think that’s led people to believe it’s a generally health promoting practice, when the research simply does not show it.
It must be the case that these microbes need the subject to be aware of their presence! Maybe the microbes have consciousness, and for the treatment to work, the microbes' consciousness has to entangle (via quantum mechanisms) with the subject's consciousness? Blind studies prevent this quantum entanglement to form, that's why the treatment stops working. We definitely need more research in this direction!
Also one issue with all of these studies is they only look at averages and don't do subgroup analysis. It may be that a few patients have an underlying condition causing depression that is highly responsive to these interventions, while it has no effect on the others.
One day people will figure out how to use these correctly.
Microbiome transplant therapy is a domain full of grifters right now who will push it to vulnerable populations desperate for hope, like parents of autistic children. The real research results are much less promising for difficult conditions.
And nobody is bothered by the story. And it gets less clicks. People get cranky when they have been suckered.
This factoid is repeated everywhere but it’s misleading without knowing that gut serotonin is a different pool than brain serotonin and they have different functions.
The brain synthesizes its serotonin locally within the brain.
It is like these armchair scientists don't understand that the actual scientists know the limits of the model system better than they do.
Science depends on accurately reporting facts, being clear about the limits of your findings, and seeking explanations that survive scrutiny. Science journalism has other priorities that are often in conflict with those of science.
Dead Comment
What's really cool is that the paper used low-dose capsaicin (just 5 μg/kg injected), and it completely restored hippocampal FOS activity and memory in older mice. Basically, that's the same stuff you get in cayenne pepper supplements - pretty easy to get your hands on.
[1] https://www.goodreads.com/book/show/28837738-the-mind-gut-co...
[2] https://www.goodreads.com/book/show/35210457-the-psychobioti...
"You can cure anything in mice."
I don't know the mechanism why, but you can find tons of papers with incredibly strong results for curing of mitigating dementia, cognitive decline, addiction, etc in mice, but these almost never seen to work on people.
The other thing concerns how potent the effect is to be therapeutic. In many cases, the effect is just marginal to be meaningful.
Conceivably parenteral capsaicin has different effects on hippocampal integrity or physiology than achievable with ingestion. I'm not familiar enough with disposition of capsaicin in the gut to comment further. My question is whether capsaicin passes from gut into the circulation in any appreciable quantity. I suspect it doesn't but I couldn't say I know for sure. I'll have to add it to the already long list of things I need to look up.
[1] https://pubmed.ncbi.nlm.nih.gov/27079706/
[2] https://pubmed.ncbi.nlm.nih.gov/31137805/
There are countless papers published where simple ingredients produce miracles in mice. Most of them don’t replicate.
If you look up most food ingredients you can find someone, somewhere claiming to have used it to produce amazing outcomes in mice. After you read a lot of those you learn not to take individual papers seriously if the claims seem too good to be true.
Can't disagree, but keep in mind that almost all meds are tested first in mice/animal models before human trials verify the effects.
Rather than jumping from one fad diet to another, just eat what you like and be sure to get a lot of fiber each day.
type A cannot have been living in humans thousands of years ago, but type B might have
type A benefits from making your brain worse at choosing healthy foods, and type B does not
Which kind would you rather have in your gut?
btw people, do drink water to keep up with the fiber. Otherwise it might not help.
Sure sounds like another fad diet.
Yeah! A fad lasting millions of years of human evolution, however.
The paper is open access. The discussion does a fine job of providing a full context for interpreting their findings.
https://www.nature.com/articles/s41586-026-10191-6
There are microbes in there that specialize in eating, say, sugar. You don't give them sugar, they send signals to your brain saying "yo, more sugar"
This is why if you go on a sugar-free diet (just stop eating candy and sweets) the cravings just go away eventually. The microbes who keep shouting for more sugar either die away or go dormant.
False. We do crave stuff. The microbiome contributes to and influences cravings, but the way you're phrasing it is misleading.
The fact that this doesn’t happen should give you pause about this woo-woo theory of cravings.
The reason you crave sugar and fat and other tasty things is that they taste good. You evolved in a world where feeling rewarded and driven to consume more of these was beneficial to survival when food was scarce.
It does some decimation, but not a full genocide.
"Why Isn't My Brain Working?"
by Datis Kharrazian
published in 2014 talked about this over a decade ago.
Edit: one of many examples: https://www.science.org/content/article/journal-retracts-inf...
I think for something this unexpected you'd want a much lower P.