Enhancing gut-brain communication reversed cognitive decline in aging mice
med.stanford.edu386 points by mustaphah 4 days ago
386 points by mustaphah 4 days ago
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]
[1] https://www.psychologytoday.com/us/blog/the-behavioral-microbiome/202404/hacking-an-individuals-personality-through-their-gut-contents
[2] https://www.abc.net.au/news/2025-07-28/faecal-microbiota-transplant-credited-with-curing-bipolar/105541522I believe this research is totally true-- I had a lot of memories come back after
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.
> 1. I stopped drinking heavily and using other drugs, i.e. marijuana
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.
This paper actually surveys research on humans and not mice.
The association between gut microbiota and cognitive decline: A systematic review of the literature
https://www.sciencedirect.com/science/article/pii/S027153172...
It shows ”Gut microbiota modulation improves cognition in adults with early impairment. Diet, probiotics, and fecal microbiota transplantation share mechanistic pathways and that evidence clarifies how microbiota-targeted strategies support cognitive health.”
The action could be explained due to an anti inflammatory action by the gut biome.
Yes, there are some interesting potential mild modulations that can occur with microbiome change.
That paper commits one of the major sins of many microbiome papers which is to attribute all benefits of diet change to the microbiome. Like the parent commenter it gets drawn to the idea that all changes in the body can be traced back to the microbiome and assumes that it explains everything, but that’s obviously not true.
However, when someone is taking two powerful substances with direct brain action and known modulators effects on memory, blaming anything else in the body is bad logic.
>Heavy alcohol use and marijuana are both known to impact memory and recall directly.
And who said they don't do this (long term) exactly through their affecting the gut microbiome?
Both alcohol and marijuana have direct actions on the brain. That’s why people consume them.
They do not exert their primary effects via microbiome modulation. This is obvious because the effects occur nearly immediately upon consumption, whereas microbiome change from what you consume is a gradual process.
The question I have is: Why has microbiome become the explanation for everything? What would lead you to believe that microbiome would be the explanation for this, when the direct action upon the brain is so much more direct and obvious? Microbiome is an interesting area of research but how did we get to this point where some are ignoring the obvious and trying to construct alternative microbiome based explanations for things like alcohol and marijuana impairing memory?
>Both alcohol and marijuana have direct actions on the brain. That’s why people consume them.
Which is orthogonal as to whether those direct actions also affect long term memory.
>They do not exert their primary effects via microbiome modulation.
Who said anything about primary effects?
a great deal of alcohol, weed, etc, is consumed ,very specifcly, to forget. to the point that users, often workers doing labour, or other jobby jobs, get fairly aggetated by days, and especialy weeks end, wrapped up in an overload of the realities of serving others interests, and ends. drugs provide a crude function similar to the processing that occurs durring sleep and dreaming. That this has effects on the gut, is hardly unexpected ,but that the system will recover with due care, is. Treating the gut as a self maintaining biological digester, which it is, then suggests looking at how various industrial digestors operate and malfunction.
Or by affecting the kidneys, or by affecting the enteric nervous system, or through some other pathway for which we have no substantial evidence of influencing memory (yet). It just seems like a baseless prioritization of a hypothesis. For some reason, people are specifically fascinated by the gut–brain axis.
>For some reason, people are specifically fascinated by the gut–brain axis.
Might the reason be that we're constantly finding new important ways it affects things, or that we see major changes to seemingly orthogonal issues from targetting the gut microbiome directly?
I think the appropriate response here is some combination of Russell's Teapot and Occam's Razor: they might, but some kind of hard evidence is necessary before humouring that theory, particularly since there's a vastly simpler explanation on hand.
It has been well recognized that alcohol significantly disrupts the bacteria in your gut.
Anecdotal. I have never drank much alcohol, but an evening Trappist helped me turn off after a day's work.
Since I stopped that habit, I do notice memory getting worse. Not saying it is THE EXPLANATION, but it is an observation non the less.
Also, getting better sleep (by fixing heartburn and meals) will mean you're more rested, and improve functioning during the day.
Your hypothesis here though is full of complicating factors.
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.
I think the "and" is for "stopped (both) A and B"
Yes, that's what they're pointing out. Changing multiple variables at once means you can't attribute changes to any one of those variables in particular.
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)
> 4 corn/20 plant oatmeal
What does this mean?
It's my own idea for a super oatmeal. Working on the idea that it's not just about having fiber in your diet, but more so about variated fiber. Each kind of fiber is preferred by a different type of gut bacteria (I'm just repeating after some hippy that most likely made that up). And the best gut biome is the most variated one. Usually pathologies stem from monocultures. Look at the most of the society. Bread, cookies, pretzels, even pizza etc. - it's all made of wheat. Sometimes you'll get oat cookies. But other grains show up in people's diets very rarely.
Here's the recipe. I'm using norwegian 5-grain oatmeal that has oats, wheat, barley, rye and spelt:
Recipe: Use two parts oatmeal (either 4-korn or 5-korn). Add one part nut mix and one part seed mix. So for 50 g of oats, add 25 g of nuts and 25 g of seeds.
Seeds: 30% flaxseed 30% chia 20% pumpkin seeds 20% sesame
Nuts: 4 parts walnuts 2 parts pecans 1 part Brazil nuts
P.S.: since most of these ingredients are pretty cheap (oatmeal used to be poor mans food), you can upgrade to Eco versions of these and get much better taste, without going that much up in price. Especially nuts.
Also, I have the nutmix and seed mix pre blended in 2 liter jars, so that I only have to mix them once a month or two.
You seem to be on the right track because supposedly for good gut health we need to eat at least thirty different plant foods each week. You've got twelve just for breakfast!
https://www.theguardian.com/wellness/2024/apr/04/30-plants-w...
https://mydoctor.kaiserpermanente.org/mas/news/eating-30-dif...
What did you do for heartburn? Just looking for ideas. I noticed reducing gluten helped me personally a lot
I stopped taking esomeprazole after being on it for 4 years, and frequently had to supplement with famotidine and tums anyway.
I had an infection and was prescribed antibiotics, and needed to pause the esomeprazole. I asked gemini about it and it suggested I take two probiotics while on the antibiotics, Saccharomyces boulardii and Lactobacillus rhamnosus GG. I noticed after a few days that I wasn't getting heartburn, and started putting the pieces together.
After the antibiotics ended, with still no heartburn, it recommend I add rhamnosus gg to the mix. So now I take all three daily and rarely get heartburn. It's been quiet a shock
There is a weak association with use of PPIs and memory loss. I myself noticed a difference once I stopped taking omeprazole regularly.
Most doctors will say avoid long term use of PPIs for a variety of reasons. Famotidine is much easier on the body, albeit less effective than PPIs.
thank you going to try this. I noticed my heartburn got a lot worse after having to take a few courses of antibiotics.
Some good notes on heartburn, a fiber regime, some combination of wheat dextrin, psyllium husk, inulin. All 3 are different and serve a somewhat different function.
Foods to eat, oatmeal, lentils.
Ginger tea, activated charcoal tabs.
Most all of that works very well to support gut bacteria so throwing some probiotics in as well can help. The gummy kind available in generic or Digestive Advantage work well!
Im not saying to live this way, but a super restrictive test diet may open your eyes to some thing and then you can add back.
I even once read that someone noticed an issue they tried to clear up for years with doctors went away on day 3 of a water fast. No, he wasn't going to fast forever. But he was shocked the first relief he ever had was that day. From there he solved his problem once his eyes were opened a bit.
I'd personally try all ground beef for a week or two. It won't kill you. Is it ideal? Probably not. But you will not have any problems from that short trial. Then add things slowly until you have a whole good diet you like.
It might not be gluten (protein) that is affecting you, but the fructans (carbohydrates) that are found in wheat, rye, and barely which are high in FODMAPs.
Look into low-FODMAP diets if you haven't already.
Thanks, my wife and I did one and it helped but it’s really hard to find the root cause because I also wasn’t eating bread at the time. I also get it from beer but not liquor, which makes me consider its gluten. Great point though, I’ll keep it in mind
It may not work for you but I had years of chronic heartburn. While sick with covid in 2020, I stopped consuming coffee and alcohol. It took a few months and for the long covid symptoms to subside, and then no more heartburn. At all. I felt really dumb that I never connected it to coffee before. I didn’t experience direct symptoms from coffee and I didn’t consume an excess amount. But it definitely was the cause.
The kind of coffee you drink can make a huge difference as well. Filter coffee is typically larger in volume so there’s more acidic liquids going in to trigger your heartburn. Compared to espresso which is usually a smaller volume. It can be a huge difference in heartburn between coffee types.
I'm a couple weeks into giving up coffee because of heartburn, and yeah, this tracks... unfortunately. I've replaced heartburn with heartache (having given up a beverage I've enjoyed daily for over 20 years).
What kind of coffee were you drinking? I replaced filter coffee with espresso and my heartburn went away.
Good luck, my friend. I’m right there with you. It’s not the physical effects but the rituals and the social connections that I miss. I felt the same with coffee as I did with smoking, which I quit about 20 years ago. It’s remarkable how much these simple vice shape our daily lives.
Yup. Discovered me and my dad have ADHD at pretty much the same time. In our case (very stimulant sensitive) we had to quit coffee to use ADHD meds. While I eventually switched to Inka (a roasted grain coffee substitute) when I saw how my heart results get better without coffee, he still struggles. He recently quit meds for some time due to unwanted symptoms and told me how he was away with some friends and deeply relished being able to normally drink coffee again.
My "chronic" acid reflux disappeared at USMC boot camp so...exercise, no snacking, no alcohol, and rigid sleep schedule?
There are many resources online on which foods trigger gerd and reflux. Also, try the whole30 anti inflammation diet, and don't eat at least 2, preferably 4h before bed.
not the commenter but I bake my own soda bread and found that i was getting heartburn from the salt that was in the recipe. once i eliminated that i could eat as much as i wanted. I also cannot eat salt preserved potato chips on consecutive days.
I kind of wonder if sometimes acid reflux happens more than we realize, but we just notice it when spicy food comes up.
Pretty sure this is correct. You only notice it when it comes right out of the top. Other days it may be 25%, 50%, or 75% of the way up. And that's still bad for your oesophagus over the long term. My dad got cancer right at the bottom and one potential cause was chronic acid reflux (GERD leading to Barrett's eosophagus).
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.
I feel that same way you described with the "fog" clearing. I don't know exactly what it is, but I'm imagining it being the fact I _finally_ get some good, restful sleep (with it taking about 2 weeks give or take for that clear headed feeling to regenerate).
Oddly I don’t feel like I sleep better, but probably do. But I’m sure you’re right about the impact of sleep as a contributor to the overall clearing.
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.
theorem of indirection, i guess.
So, you stopped being an alcoholic and pothead, and your memory improved?
Wow, it must be those gut microbes!
What unnecessary snark. Is a little civility too much to ask for?
In my opinion, gut microbiome stuff is massively overhyped.
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.
Here's a meta analysis of 12 studies showing that FMT has a significant effect in reducing depression:
https://pmc.ncbi.nlm.nih.gov/articles/PMC12536323/
It also found the effect was greater in people with IBS.
I wonder how that study would fare against a double blind where some people get FMT and others do not, but they are both given the same attention and care otherwise over the course of the study?
This meta-analysis isn’t very convincing. Most of the studies included were primarily about other measures like IBS, COVID-related GI symptoms, or Fibromyalgia. Improving GI problems would be expected to improve mood.
The positive result is heavily driven by an outlier study on Fibromyalgia that has results that look a little too suspicious relative to the other studies.
> Improving GI problems would be expected to improve mood.
While improving GI problems might improve your mood, I don't think it is accurate to equate depression with "bad mood".
A friend of mine has IBS and while her GI problems are under control most of the time, she still gets hit hard by depressive episodes.
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.
It certainly anecdotal, but feels like you can positively effect your gut microbiome for example by riding a horse. Ive read research about how other mammals can share their microbiomes with humans, if its not the horses biome then what is it that so satisfingly calming post ride. Would love to be enlightened. Ride a horse if you need to destress, amazing creatures.
It certainly anecdotal, but feels like you can positively effect your gut microbiome for example by riding a bicycle. If its not the bike's biome then what is it that so satisfingly calming post ride. Would love to be enlightened. Ride a bike if you need to destress, amazing machines.
https://www.frontiersin.org/journals/cellular-and-infection-... https://www.cell.com/iscience/fulltext/S2589-0042(25)02209-6 https://www.sciencedirect.com/science/article/pii/S235277142...
im talking about impacting your microbiome through another animal, not the short term effects from aerobic exercise or BDNF and what that feels like. this experience didnt hit quite like other typical metabolic functions.
great to hear you like BDNF. we all could use more of that.
These articles talk about subtle changes to one's microbiome by cohabiting with animals and trading microbes with them. That's a process that takes place over months if not years.
Meanwhile, you suggest that such microbial influence must be reason you feel calm right after riding your horse.
I don't think I need to further explain why it's a ridiculous claim.
i guess in that case, washing woth soap everyday is probably a negative factor?
Washing with soap everyday unless you are very dirty is indeed negative and can dry your skin. Especially as most of what is called soap now is not soap but a very complex collection of synthetic organic chemicals.
Exactly how negative it is though is difficult to determine and probably varies from person to person.
I like this measured take, but I think we can also expect it to be a virtuous cycle.
Sure, you have to put in a lot of effort to get the system starting, but eventually the feedback loop pays dividends that outweigh the principal.
Everything else about the human body seems to be this way, adaptation or maladaptation.
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.
You are probably right on the specifics, but serotonin is produced/located in the gut, and its an incredibly important neurotransmitter.
One day people will figure out how to use these correctly.
> but serotonin is produced/located in the gut, and its an incredibly important neurotransmitter.
Serotonin in the gut doesn’t go to your brain. It serves a different function in the gut.
The brain synthesizes serotonin inside of the brain. It doesn’t come from your gut.
Thanks for following up with a correction. This is a myth that simply refuses to die. I cannot even count the number of times I’ve heard people repeating it.
There was a South Park episode about this years ago where everyone was trying to get it from Tom Brady.
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?
You either need a lab to test donor samples first, or when this was more of a craze, a popular source of 'donations' for the DIY crowd was young children.
If you're interested in digging into the people that were doing this, they had a website dedicated to everyone telling their stories of how they went about their own individual journeys.
The website was called thepowerofpoop.com and looks like it's gone now, but is available on the wayback machine including individual articles and images.
I would go back to at least 2022 .. I think they possibly got in legal trouble at some point and started taking things down.
Fecal transplants...people will do anything to avoid eating a balanced, largely/wholly plant-based diet with a wide variety of fruits and vegetables.
I think the idea is that the biome is built up over time and you can't always just eat your way to certain bacteria growing in your gut.
I think the fecal transplants help to essentially seed your gut with healthy bacteria, which makes adapting to the proper diet easier when your body isn't constantly fighting you.
It's not that simple.
The last couple years, a buddy of mine did exactly what you proposed: He had massive GI problems, so he started watching what he ate, and… his problems became much worse.
Fast forward to a couple months ago, when he sees a doctor specializing in this stuff and she tells him to significantly reduce plant-based food for a while "because your gut biome isn't able to handle it right now. You should go eat a burger every now and then." So he's been following her advice and all of sudden he is without any GI issues whatsoever.
My buddy got lucky (found the right doctor, could eat his way out of it) but if your gut biome is seriously out of whack, I can definitely see the appeal of an FMT to kickstart your recovery.
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.
There is zero evidence that poop transplants have any effect on autism, let's be clear here.
Not true; their clinical trials[1] finds Improvements in GI symptoms, ASD symptoms, and the microbiome all persisted for at least 8 weeks after treatment ended, suggesting a long-term impact[2]
More recently, a study finds The modulation of the gut microbiota using MTT in ASD has shown beneficial and long-term effects on GI symptoms and core symptoms of autism[3]
[1] https://gutbrainaxistherapeutics.com/pipeline/#clinical-tria...
[2] https://link.springer.com/article/10.1186/s40168-016-0225-7
[3] https://www.tandfonline.com/doi/abs/10.1080/19490976.2025.24...
There are a lot of HN users that think they are better at science because they know about p-hacking and the limitations of animal models.
"Reversing memory loss in mice via gut-brain communication"
And nobody is bothered by the story. And it gets less clicks. People get cranky when they have been suckered.
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.
Most of the serotonin we produce comes from our gut.
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.
Serotonin from the gut affects vagal neurons. They carry that signal directly to the brain. That has a significant effect on up and down regulation of mood and arousal.
Okay that’s like my company that uses Salesforce that sends an invoice to another company that also uses Salesforce.
The fact that we both use Salesforce does not matter. It’s internal and doesn’t mean anything outside the company. Both the brain and gut re-used the molecule for their own internal signaling. Evolutionarily it was cheaper to use an existing molecule.
To the brain, the invoice is just “I’m full” or “I’m hangry.” It doesn’t care how much serotonin the gut had to produce internally to issue that “invoice.” The brain will produce its own serotonin from the signal of satiety but it won’t give you any more than you can from just feeling full.
It is a powerful neuron hormone. The mechanisms are different. It is still important to recognize the rather dramatic influence this has on the brain. That was what this article was about. This pathway can easily lead to depression and significant broad down regulation in the brain. Serotonin inside of the brain works very specifically. The vagus nerve signal has a very broad impact and should not be hand waved. If your vasovagal system has dysregulation it can lead to all sorts of specific brain internal negative outcomes systemically. I think your model of how this works is not very accurate regarding how broadly connected the vagal signaling pathway is and how that impacts how your brain functions.
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
See: vagal neurons and vagus nerve. Serotonin from gut directly impacts those. Your brain still directly interprets that signal from the vagus nerve and uses that to up and down regulate mood and arousal. Impact is still significant
Your nervous system extends over your entire body, the brain doesn't live in a firewalled jar.
To extend the metaphor, the brain may have a robust firewall, but it also transacts with millions of clients over a separate (electric rather than chemical) network.
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.
I bet it started with people trying to 1-up other commenters via the usual “achtually…” and then proceeding with the “in mice” notice.
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.
In this case, it was in the headline of the article. I don't know how much clearer one would expect it to be.
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.
[1] https://www.goodreads.com/book/show/28837738-the-mind-gut-co...
[2] https://www.goodreads.com/book/show/35210457-the-psychobioti...
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.
Chili could work [1], but not too much of it [2]
No 2 is a fascinating study! My mother was 'taking' (eating) large amounts of raw chilli as she found it a very efficient cure for her rheumatoid arthritis - she had brilliantly reduced joint pain. BUT after a few years it caused painful and disfiguring rosacea.
She stopped the chilli and moved to acupuncture for the arthritis, which worked pretty much as well, but not something she can do herself at home for 'free'.
Since she has v low BML, I'm now pleased to see she stopped eating too much chilli!
> 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.
> After you read a lot of those you learn not to take individual papers seriously
Can't disagree, but keep in mind that almost all meds are tested first in mice/animal models before human trials verify the effects.
My comment had nothing to do with mice versus humans.
It’s about singular papers with too good to be true results. You can find these in humans too.
I guess "too good to be true" is not a decent argument to convince a rational mind
The salient point of my comment is singular paper
The rational mind should not be seeing singular papers and assuming they’re correct. There are a lot of incentives for researchers to publish amazing results that benefit their career. They find ways to publish these through small sample sizes, p-hacking, or worse like faking results.
The amazing results usually disappear in larger studies by more rigorous researchers. There are so many papers showing amazing things in a handful of mice in a lab or even human volunteers that do not appear again in properly powered studies.
That's a fair clarification.
I never said we have sufficient evidence to act. But "too good to be true" + "singular paper" together can become an unfalsifiable dismissal - by that logic, every important result looks suspicious before it replicates. The interesting question is what priors should update our confidence here.
Stanford/Arc Institute and published in Nature + mechanistic grounding + prior research on gut-brain axis gives me way more confidence than average, but you're right, that's not nearly enough for most, but quite sufficient for me, and surely others with informed priors or a strong motive.
> by that logic, every important result looks suspicious before it replicates
Every important result should look suspicious before replication. This is the rational way to interpret early research.
You should not allow your mental probability distribution to be anchored around the first claim you see that is proposed as a paper. In the modern publishing environment, a heuristic of assuming singular results will not replicate would be accurate more often than assuming they’re true.
This isn’t intuitively obvious until you’ve read a lot of papers. It’s unfortunate but true.
Even some of the widely accepted findings like the benefits of fish oil supplementation are having a hard time replicating in large scale studies. Go back 10 years and it was almost universally accepted that those early fish oil studies must 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
Which kind would you rather have in your gut?
To do this eat stuff that grows and not further processed.
Don't be simplistic. Mold on old bread grows and is natural, yet you should not eat it all day.
> you should not eat it all day
How sure are we about this? How certain are we that those specific species of mold have a net negative effect, rather than a net positive (like for example mushrooms)? Penicillium grows on stale foods and I doubt eating it would have a net negative effect.
>I doubt eating it would have a net negative effect.
Feel free to eat it.
"Penicillium Species and Their Associated Mycotoxins" - https://pubmed.ncbi.nlm.nih.gov/27924532/
Muchrooms have mycotoxins too. And red meat is a carcinogen. And predator fish have plenty of heavy metals. And the list goes on and on. Yet we eat all those things. Hence the "net positive".
Let me also introduce you to the new kid on the block, the resistant starch: https://www.youtube.com/watch?v=U6IcMW5Khh4
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.
The post is about a scientific study and your response is your opinion with nothing else to back it up?
they IMO are trying to help by giving good ideas to keep a healthy gut. Add that to the study and at least to me, it´s a nice idea.
btw people, do drink water to keep up with the fiber. Otherwise it might not help.
> eat what you like and be sure to get a lot of fiber each day
Sure sounds like another fad diet.
> Sure sounds like another fad diet.
Yeah! A fad lasting millions of years of human evolution, however.
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.
> "You" don't crave stuff
False. We do crave stuff. The microbiome contributes to and influences cravings, but the way you're phrasing it is misleading.
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
> Good taste is an incentive to satisfy something more primary,
Covered in my comment above: The more primary drive is that those are high calorie foods. A drive to consume more high calorie foods is beneficial in times of food scarcity, like the past.
Antibiotics don't kill 100% of the gut biome, if it did so, we'd die.
It does some decimation, but not a full genocide.
Cutting sugar doesn’t kill 100% of the gut biome either. It doesn’t kill gut biome at all, actually, it just changes some of the proportions. Those parts of the microbiome are most likely still there, just in different ratios.
Antibiotics are a far more powerful and faster modulator of gut biome, therefore if the above was true we’d see similar effects occurring more rapidly with antibiotics than diet.
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.
Heraclitus — 'For the best men choose one thing above all—immortal glory among mortals; but the masses stuff themselves like cattle.'
Very well done study with a cautious interpretation of potential translational relevance in humans.
The paper is open access. The discussion does a fine job of providing a full context for interpreting their findings.
That makes sense. I am of the opinion that the gut-brain connection exists. It is real in my view. A healthy gut promotes better mood and health. A parasite-ridden gut leads to all sorts of issues, including anxiety, irritability, stress, constipation and its counterpart, cancer and mental decline. I am doing a gut cleanse now to rebalance my intestinal flora and hopefully remove any bad actors from my gut resulting from years of ingesting processed foods. Want to make sure no parasites accompany me on my upcoming medical imaging visit.
The book
"Why Isn't My Brain Working?"
by Datis Kharrazian
published in 2014 talked about this over a decade ago.
I smell bad data. This sounds too good to be true and most studies of this kind have turned out to be false a few years down the line.
Edit: one of many examples: https://www.science.org/content/article/journal-retracts-inf...
It doesn't seem to link to any data at all so we can't check, but I wouldn't be entirely surprised if they used the "standard" P=0.05.
I think for something this unexpected you'd want a much lower P.
Great info. This is one of those things that it is much faster for an individual to take into their own hands to prove out, rather than waiting for the system to provide us with an answer. Too many decision makers who are unlikely to all be aligned with our own individual interests.
For those who may be interested in learning more about the gut and how it affects your body and brain, this is a great, accessible, read
https://www.amazon.com/Gut-inside-story-bodys-under-rated/dp...
Also, while we're on the topic, if you ever find your self at the other end of the world in Tasmania, I highly recommend a visit to the MONA museum, which houses the Poo Machine.
https://www.abc.net.au/news/2017-11-07/mona-poo-machine-join...
i like how this research (and others related) kind of supports the idea that free will might be lacking. I still keep a pinch of skepticism about this idea, understanding that it's just a concept. But personally i like it, because it even fells a bit relieving... not to say that it helps you abandon responsibility, but it makes your stance on life easier, and pushes you not to blame yourself too much for your weaknesses.
What is free will? In Friston’s predictive processing framework, free will isn’t a force that stands outside the brain and overrides it… it’s what the system calls the experience of higher level predictions outcompeting lower-level ones. The brain is a hierarchical prediction machine constantly minimizing surprise, and what feels like a decision is the resolution of competing models, where your prefrontal self model of who you are and what matters generates a stronger attractor than the opposing signal. The sense of “I chose this” is likely a post hoc narrative the DMN constructs after the resolution has already occurred.. agency as story rather than cause. There’s no ghost in the machine, just a very sophisticated model of a self that includes the prediction that it can choose.
Through the vagus nerve and serotonin availability, a dysbiotic gut amplifies lower level threat and conservation signals, making them harder for higher level prefrontal predictions to outcompete. What feels like weakness of will may partly be the system running on a degraded substrate… the DMN then constructs a story about discipline and character over a causal chain that started in the enteric nervous system.
So, you can’t even really perceive some of this. But you essentially can’t overcome it either. The decisions are made before you thought about it.
"It's not my will, it's the will of the bugs in my butt!" yes, very "relieving."
I kid, ;) but I see your point. The idea that you might, say, struggle to resist candy and sweets and it's because some population of your gut biome is fighting for its life if you don't eat sugar... makes sense.
The idea that "I just cut sugar out for six weeks and my willpower to resist sugar went through the roof" ... not because your willpower changed, but because you killed that part of your gut biome.
Unless I misread, I found interesting that exposing young mice to old-mice bacteria makes them behave old, but exposing old mice to young-mice bacteria doesn't make them behave young. I wonder if there is something in old-specimen bacteria that wins over young-specimen bacteria.
Maybe this explain it:
https://www.psypost.org/scientists-just-discovered-that-a-hi...
Article doesn't mention any particular foods that would help.
Is it the typical, eat more fiber, more non-processed, Mediterranean? And this is just showing yet another thing that diet impacts? A link exists, but no specific types of diet to help with aging?.
> They showed that colonizing the guts of young mice with this bacterial species inhibited their performance on the object recognition and maze escape tasks, and that this deficit correlated with a reduction of activity in the hippocampus.
I suspect if my guts were forcibly colonized against my will that I might suffer inhibited performance in quite a number of areas.
unrelated but maybe interesting...
I had a colonoscopy and had to empty my system.
I had 1/2 gallon of this fluid to drink the night before, and the other 1/2 gallon to drink the day of. At that point my digestive system was empty.
I will say with an empty system I felt energized and a lot more clearheaded.
I wonder if doing this from time to time is helpful to your system, and furthermore if eating smaller portions would be helpful to my energy levels.
Try intermittent fasting. It's easy. It gives your gut a chance to rest. For me it helped with weight control and slightly improved my overall well being. Later I also eliminated sugar from my diet and reduced caffeine intake to minimum by replacing coffee with reasonable amounts of quality tea. That in turn improved my mood, made me less angry and emotional. I also started exercising a bit. All of that combined increased my energy levels, made me calmer, nicer and a bit more optimistic and happy.
>they treated old mice with a molecule that activates the vagus nerve
Anyone know what molecule and treated how?
I got into bicycle touring a few years ago, and it’s an ultra-endurance activity which means burning 3- 4 times as many calories as I would on a sedentary day. My training rides were all local weekend overnighters in preparation for the big 1000 mile challenge ride, and they were no big deal.
On the big ride, about 3 days in I started experiencing bouts of intestinal distress which would put me into some of the blackest moods I can recall experiencing as an adult. My whole thought process broke down and I became ruthlessly nihilistic about everything. I was ready to tell my partner to go fuck himself, chuck my bike off a bridge and take an uber to the nearest airport.
But then when the intestinal distress subsided I came back to my senses and I was like “WTH was that all about?” It happened several times, to varying degrees of intensity over the 10 day tour. My eating strategy improved and I bought some cannabis which helped my manage the issue and I was able to complete the tour.
That was a few years ago and I’ve never experienced the black mood again. It has prompted me to believe that the mind-gut connection is much stronger than we might have been giving it credit for, and if you suffer from mood or cognition issues, big or small, you may want to investigate whether your guts and gut flora might be playing an influential role.
What you experienced was the gut-brain axis failing under extreme metabolic stress in real time. 3-4x caloric demand and your enteric nervous system was under enormous strain dysregulation of serotonin production, inflammatory signaling flooding the vagus nerve upward into brainstem arousal states, directly degrading the prefrontal predictions that normally keep your self model coherent and future oriented. the nihilism wasn’t a psychological response to difficulty it was your predictive hierarchy collapsing from the bottom up, the higher level model of who you are and why this matters losing the competition against overwhelming lower level distress signals. The fact that it resolved when the intestinal distress subsided is actually clear indicator that mood and cognition are downstream of gut state more than we like to admit. our gut makes a like 80% of our serotonin or something
Yogurt and pickled things acquired.
You are what you eat.
Now I only need to find out how to use the 387 gut coprocessor in my belly to crunch those floats.
#include <gpu_control.h> // g stands for gut
... in mice. So if any of this held in humans, I think you'd see reversal of old-age memory problems in people treated with antibiotics that kill Parabacteroides goldsteinii.
As far as I know, no such effect has been observed.
And this article claims inflamation from that strain, the NIH claims otherwise: "Parabacteroides goldsteinii is a next-generation probiotic gut bacterium with significant anti-inflammatory and metabolic benefits, often reduced in obese or diseased states. "
It's possible the specifics are different but that the overall idea still could work for humans. It seems worth at least exploring.
Probably not worth exploring. I've seen "breakthroughs" for dementia/cognitive decline like this for the past 25-30 years.
Not a single one of them has gone anywhere.
incoming GPL4
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in mice is clearly in the subhead.
The connection between gut-brain has been studied in humans, as well as the effect of diet and gut bacteria on brain functions.
And in this case it sounds like the pathway to determining if this has an effect in humans as well might be relatively short given there is a pool of patients receiving vagus nerve stimulation for other things that might provide data.
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So drinking turpentine will cure my homosexuality?
Mice mice mice. Tell me when you test on humans
In theory you would never test on humans directly. You would go through various order testing and slowly work your way up to a final verification on human subjects that has almost no chance of going wrong and that the worst possible outcome is that nothing happens.
We there yet?
> Importantly, vagus nerve stimulation is approved by the Food and Drug Administration as a treatment for depression or epilepsy and to aid stroke recovery.