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]
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?
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)
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
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).
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.
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.
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.
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).
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.
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.
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.
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.
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?
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.
>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!
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.
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.
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.
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.
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.
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 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]
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.
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.
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
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.
> 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.
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.
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
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.
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
"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.
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.
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.
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.
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.
> 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 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.
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.
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
... 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. "
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.
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.
> Importantly, vagus nerve stimulation is approved by the Food and Drug Administration as a treatment for depression or epilepsy and to aid stroke recovery.
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?reply