Gut–Brain axis | Hacker News Reader

Gut–Brain axis

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160 pointsyamrzou54 comments

I always wondered how much conjecture this was but a few years ago I had severe IBS problems when I would get very nauseous about 30 mins after I ate among some other gut stuff Ill spare you details on. Got every test done, saw multiple specialists who willing to try anything to help me. Nothing was helping.

Finally went to a specialist who said “I think I know what’s wrong with you. Take these 2 tests and if both are negative for another condition i have a medicine to start you on. “

Tests came back negative and he prescribed something called Nortriptyline. It’s a 1970s anti depression medicine they dont usually prescribe anymore because of the side effects at the dose to affect mood (150-200mg). However, at small doses (25 mg) it can solve a lot of pain and gut malfunction problems. When I started it, I immediately got positive results almost like taking an ibuprofen for a headache. I was 5’11’’, 130 lbs before and from the pill, lifting weights, and fight training I got to 200 lbs and in the best shape I’ve ever been.

My sister in law is also on it for her back at a low dose and it’s the only thing that helps her.

This cheap pill was a miracle for me. I now believe in the axis and see the real connection between the brain and the gut.

What’s the idea for why it helps your sister’s back problem?

My answer would be trash because I don’t quite understand it, except to say it seems to regulate some common chemical pathways in the body. The way it was explained to me is that it clears up a bad signal between the brain and nerves, particularly in the gut. My gut was just overreacting to any food put in it and the pill helps restore normal “talk” between the brain and the gut. Every other doc was trying to treat my gut to make it better which is logical - this other specialist used my brain to fix it.

I know the back thing isn’t gut brain axis but I just figured I’d mention it.

The gut also has a nervous system, it's like a second brain. So the drug might have targeted just the "brain cells" of the gut, and your recovery might have nothing to do with an "axis" between gut and real brain. Note, IANAMD.

Do you need to take that chronically or have you reached any sort of remission where you don't need to take it forever?

I cannot speak for OP's sister, but I personally feel gut problems in my back. There is no medical explanation for that, that I am aware of. But when I eat certain foods, I have intense back pain the next day.

The only reason I think it is related to gut problems is because the back pain is perfectly correlated with certain foods (e.g. large amounts of gluten, smoked meat) and has 0 correlation with normal reasons for back pain.

It could be inflammation making the joints unhappy. You could do worse than get some blood tests done for CRP.

Nortriptyline is used for neuropathic pain.

Now you got me thinking about the idea of "gut brain" depression just like our normal brains can get depression...

An interesting thing to think about, science isn’t really sure why SSRIs work the way they do on depression [0]. The effect of the SSRI on brain serotonin is immediate, but the drugs take 3-4 weeks to actually have an effect on depressive symptoms.

There is a suspicion that SSRIs may change the gut microbiome, and that’s why it has an effect and why there is a time delay.

[0] https://www.discovermagazine.com/health/how-antidepressants-...

Are there any other credible hypotheses for why SSRIs take weeks to affect mood according to the literature, when their effect on the serotonin is immediate?

Yes, another is that they cause an increase in BDNF in the hippocampus, which stimulates neurogenesis there. This process of literally growing neurons takes weeks, even months.

Actually SSRIs usually have an immediate worsening effect, which then gradually resolves by week 3-4.

The same drug also had immediate effects for me when I was getting daily migraines a few years ago.

do you happen to know what the other two tests were / what the other condition being tested for was?

> I was 5’11’’, 130 lbs before and from the pill, lifting weights, and fight training I got to 200 lbs and in the best shape I’ve ever been.

Very curious about this.

What were your IBS symptoms before taking Nortiptyline?

People are wowed by animals that have multiple brains (eg: octopus' arms), perhaps not realizing that humans do too, in a sense — the enteric nervous system (described in the article).

It's the reason you can still digest food if you're a quadriplegic, for instance.

The enteric nervous system has about the same number of neurons as a cat brain, for point of reference.

Sometimes I think of the activity of my guts as my little cat brain, taking care of things down there, so I don't have to (:

Also, if you're interested in what intestines look like squirming about in real time: (beware! NSFW, medical gore, blood/guts/etc) https://old.reddit.com/r/medizzy/comments/ttz995/peristalsis...

Gross, but fascinating too.

>beware! NSFW, medical gore, blood/guts/etc

Same for a human brain, or heart, whether pumping or not. Comment based on seeing a NatGeo photo of a human brain (not a diagram), and a real human heart in the hand of a medical student friend of mine, at his college exhibition.

The brain photo grossed me out more than the real heart; don't know why. :)

Edit: the heart didn't gross me out at all, actually.

Wow that’s great! Reminds me of the Cerebretes in StarCraft, long fleshy undulating coils

I am 100% positive that is the gut brain that is listening to my microbiota saying that yes I should buy those chocolates in the grocery store and no I will not eat them all in one sitting. My head brain knows better but with that confident voice speaking differently what am I to do?

Are you certain there’s only a single consciousness operating in your head?

Heck no!

And if you're interested, check out the Nobel-prize-winning split-brain experiments. Example: https://www.youtube.com/watch?v=aCv4K5aStdU

The master and his emissary already make up two, and as someone said once “the reason why inside you there are two wolves is because the smaller wolves have to merge into coalitions to have a chance of getting first past the post in the race for control of your muscles.”

I’m not sure I have anything too enlightening to add, but my anecdotal experience with IBS resonates with this.

I have gotten my IBS under control through a variety of ways, but perhaps my first realization of this was around 15 years ago. I had not received much help from my doctor or gastroenterologist, and back then, gastroenterologists did not like to approach IBS at all, because it’s a tricky syndrome and their training at the time didn’t have much to offer.

At some point, I noticed that it was a two way street between anxiety my IBS. If I was having anxiety, then I’d often start having digestive problems. If I started having digestive problems, I’d also have increased anxiety. This was first apparent to me around traveling, because all of the hustle and bustle of getting through airports was an anxiety trigger, and I w was simultaneously disrupting my diet, causing an IBS flair every time I went somewhere.

Back then, I had been reading about the potential positive effects of cognitive behavioral therapy for IBS. So I began to practice awareness and some simple CBT, anticipated by knowing I’d be anxious about traveling.

Much to my surprise, it helped immensely in that particular scenario. It’s hard to have that level of emotional awareness all the time though.

In case it helps anyone, I’ve tried a ton of things over the years. The things that have helped me most are - probiotics (histamine degrading), soluble fiber supplementation (acacia root) and low histamine diet.

Similar experience, IBS + anxiety combo knowing me out on the daily. CBT was also the only thing I've tried which I would say had a positive long-term and measurable improvement.

(In the UK, CBT is a common treatment for IBS and free with the NHS. It was never recommended to me in Australia, and had I known, I would've sought it our far earlier in life.)

Fascinating - "rest and digest" is after all the opposite of fight-flight.

I wonder if your nervous system is the weak link, in the same sense that a cold or flu generally knocks you for a six in largely the same specific way. Sounds like it buckles under load to a statistically pathological extent (from a practical standpoint of "this is not helpful and is disproportionately slowing me down"). Mine kinda does too. Still looking into how to improve it beyond just simple anxiety management.

Thanks for all this info! I’ve got a different gastro issue (eosinophilic esophagitis). Who knows if it’ll work or not, but high histamine foods overlap with food triggers for my symptoms.

I also noticed correlation between higher stress work events, and symptoms, but wrote it off as coincidence.

Who knows if it’ll work, but it’s definitely worth a shot!

What I always thought was interesting was that when you take psychedelics, despite whether it's mushrooms, LSD, or 2C-B (and what have you), you can feel this little ball of energy in your stomach (particularly noticeable when starting to come up) that persists for most of the trip.

My woo-woo theory is that there's some kind of serotonergic activity happening in the gut (which is responsible for some ~95% of the body's serotonin production) that is so profound you can physically feel it.

Your gut has it's own nervous system and sensory nerves including taste buds. I think the burden of proof would be on explaining why it's doesn't trip balls.

How do/would we know it doesn’t?

The main receptor for LSD is the 5-HT2A receptor. There is a ton of 5-HT2A receptors in the gut, mainly an enterochromaffin cells.

The amount of 5-HT2A receptors expressed in the intestine increases as you go down the length of the intestine.

My mother is a dietitian and she started a podcast this year where she’s talked a lot about the microbiota and how it affects our organisms in a lot of different ways.

For instance, did you know that bacteria in our guts help us “digest” and expel heavy metals?

In the third part of the episodes about the microbiota[0] she talks about the gut-brain axis:

> l’intestino può comunicare al cervello uno stato di disagio o disbiosi procurando, oltre al gonfiore, anche un possibile stato d’ansia o abbassamento dell’umore

that translates more or less to:

> the gut can communicate with the brain a dysbiotic state causing, in addition to swelling, a state of anxiety

The podcast is in Italian, but the transcriptions can be easily translated in English.

[0] https://dietista.it/2023/03/29/e-la-pancia-non-c-e-piu-terza...

I know someone who has crippling anxiety at a level that requires medication. She has always stated that when she has any stomach issues, it increases the risk of any panic events. Additionally, she found that consuming a daily probiotic reduces her baseline anxiety.

The more we learn about it (this article included), and change variables in our lives, the more certain we are that all types of non-gut-health metrics can be improved by improving gut microbiome.

I developed a panic disorder over the pandemic. Did all the things—meditation, therapy, vitamins, minerals and medication, in that order. All of them took more and more of the edge off, but it wasn't until I started an SNRI that I was able to better pull the signal from my gut. It turns out I have at the very least non-celiac gluten intolerance. Once I went on a strict gluten free diet practically all of my physical and mental symptoms have vanished.

Now, when I consume something with gluten accidentally, I'm met with pretty much all of the fun depression, anxiety and physical pain I was feeling before. Our gut health influences _a lot_ more than we probably realize.

The microbiome for the baby comes from the mother as it passes through the birth canal or in the case c-section to a lesser degree via breast feeding - bootstrapping us for healthy digestive tract.

Of note - it is common for mothers to receive antibiotics during delivery for a great many reasons. This can delay the development of the gut microbiome in babies, and is potentially linked to colic.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170024/

In some c-section cases they’ll perform “vaginal seeding”, wherein the microbiome from the mother’s vaginal canal is swabbed onto the face, mouth, etc. of the newborn.

https://my.clevelandclinic.org/health/treatments/22096-vagin...

I first learned about Gut-Brain axis at a meditation school. About a decade ago. They pointed out clearly that there are neuron like cells in the gut region, and they are directly connected to the nervous system.

They didn't have any scientific proof, but I believed them. Their reasoning was on point. Fast forward a few years, Duke publishes a video[1] on the topic. And these days, I know dieticians and medical professionals who actively look for food anomalies to fix emotional issues and stress.

[1] https://www.youtube.com/watch?v=oym87kVhqm4&ab_channel=DukeU...

This article asserts that the gut-brain axis model theory is more than just a theory. But AFAIK, this has yet to be demonstrated medically, via FDA-approved therapies that treat the brain by changing the gut. Thus the idea is intriguing, but IMHO, unproven where it counts, in treating and curing sickness.

I certainly hope it's more than a hypothesis! [1]

If true, this could potentially provide breakthroughs against Alzheimer's, Parkinson's, autism, and a whole host of other diseases.

[1] I know hope isn't science. But let's give the investigators plenty of money to continue this research. This is the most promising new line of thinking we've had towards solving these diseases in my entire lifetime. beta amyloid, tau, and the rest haven't gotten us anywhere.

We also know that science doesn't do a very good job when it comes to long term effects on human beings. They took awfully long time to declare that smoking is bad, despite plenty of evidence. Same goes for alcohol. They have still not figured out fat, carbs, sugar etc.

I feel, science when it comes to directly observable and measurable systems works pretty well and is accurate. However, when same is applied to systems which are not lab controlled/controllable (like human diet) then it really hard to prove of disprove anything. We are better off believing things which are proven in practice than believe bigpharma funded studies which can be (and are) manipulated by fudging, manufacturing and/or simply twisting data.

Science is a method/study, not an isolated entity. Who is "they"? You mean "scientists"? Which ones? The ones paid off by Big Tobacco? Often the negative issues we face are ignored due to conflicts of interest, bias, and societies/economies valuing certain things (wealth of few) over other things (health of many). That is not the fault of "science".

I'd cut scientists some slack here. People often forget that almost all of the actually useful and used medicine is less than 100 years old; that almost all that goes into items of everyday life is less than 100 years old too. Cigarettes in the form we recognize today are less than 200 years old, and for most of the time since then 'till now, neither medicine nor biological sciences knew shit about anything, or had any useful equipment to measure anything.

The exponential progress of technology isn't just the Internet and rockets and GDP. It's all knowledge and all tools derived from it, many of which are necessary to make further scientific advances. Arguably, all that's useful has been invented or refined in the last 200 years, with the distribution leaning heavily towards the present.

So yeah, it took scientists a while to declare that smoking is bad. There were many reasons for it, but a major contributing factor was that they had neither good models nor good tools until very recently.

It cites multiple studies though. E.g. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367209/

Just because there are not currently any FDA approved medicines doesn’t mean it isn’t science. I also would push back at anyone asserting government approval is required for science to be accurate.

100%. FDA approval is nonsense. FDA plays in arms of big pharma to provide you good advice which also makes money. They hardly peddle any advice which doesn't make money. For instance, linkage of cancer, heart disease, kidney disease etc with processed foods, sugar, fructose (fruit juice, corn syrup) etc despite tonnes of contrary evidence

Nah bro, this is just like all rare cancers and orphan diseases, which are also fake. If they were real, the FDA would be on top of that.

Get a load of this literature review on the gut brain axis from pages 88-137, 49 pages listing over 1694 totally bogus citations: https://journals.physiology.org/doi/pdf/10.1152/physrev.0001.... There's clearly no epistemological basis for this stuff!

(\s)

I believe the opposite is actually applied in practice, e.g. prescribing antidepressants to people with IBS for instance where the physical cause of the bowel symptoms isn't obvious/is suspected to be neurologically related.

From the point of view of somebody with IBD, negative cognitive effects in the middle of a flare seem pretty "common sense" obvious but it could also be down to dehydration etc... But that's in the case where there is a specific physical gut disease process in progress. I imagine that treating mental health conditions by altering the gut in people who have healthy bowels is probably a dead end.

I'll challenge that, to me this is a no-brainer with mountains of evidence.

You can look at research about using antibiotics or fecal-matter transplants and outcomes on both physiological and psychological health.

Too many to list for antibiotics and host health:

https://scholar.google.com/scholar?hl=en&as_sdt=0%2C10&q=ant...

Here's one about treating metabolic syndrome with fecal-matter transplants to cause a shift in host microbiome

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045147/

  "The human gut microbiome is recognized as an independent environmental modulator of host metabolic health and disease. Research in animal models has demonstrated that the gut microbiome has the functional capacity to induce or relieve metabolic syndrome."

How is that different from saying that there's an arm-brain axis, because breaking your arm causes psychological effects, and treating the fracture alleviates these effects?

The question is if you can treat the brain by doing something to a healthy arm, or vice versa.

It's good to be skeptical, but my wife works in this field and I can tell you that there's a lot capital flowing to this area of research, and a substantive body of research that supports it.

You could also layer the emotional / sexual subsystems on top of the gut one.

Say more?

I had some ~data about how sexual pulsions are really deeply integrated with your GI system

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