Serotonin Production (gut) Depends On Bacteria

[narouz]

Yes, very interesting, haidut!

We show that twice daily delivery of antibiotics by gavage depleted mice of their cultivable fecal microbiota and reduced the fecal bacterial DNA load by 400 fold while ensuring the animals' health.

I wonder how long it took the mice's biome to return to normal
Or if it did, indeed, return to something like it was before the experiment.

Mice subjected to the protocol for 17 days displayed enlarged ceca, reduced Peyer's patches and small spleens.

I wonder why their cecums (I guess "ceca" is the plural) enlarged.
And why their spleens shrank (I don't know much about spleens).

Perhaps the most important finding here is cholate and deoxycholate, both of which are released by the liver/gallbladder to stimulate fat absorption. Since these metabolites transiently (but powerfully) stimulate serotonin synthesis, it may provide yet another explanation why Peat tries to steer away from fat, and why high fat diets are carcinogenic. I wonder if there is a study that compares the effects of different types of fat on cholate release. It would be a major win for Peat if PUFA stimulates a lot more cholate release than MUFA and saturated fat.

Yeah, this was the obvious question for me.

Some bacteria that can be used for colonizing the gut does NOT have stimulating effect on serotonin synthesis.
"...We demonstrate that indigenous spore-forming microbes from colons of SPF mice (Sp) and from a healthy human colon (hSp) sufficiently mediate microbiota effects on colonic and blood 5-HT. While we show that B. fragilis, B. uniformis, SFB, ASF, and a consortium of Bacteroides species cultured from mice, including B. thetaiotaomicron, B. acidifaciens, and B. vulgatus, have no effect on host peripheral 5-HT (Figure 3), whether other non-Sp microbial species or communities are capable of modulating colonic and serum 5-HT remains unclear."
So, people taking antibiotics for whatever reason can then attempt to re-colonize with these bacterial strains as a more permanent way of lowering their serotonin synthesis.

And here we're into the world of the gut biome
as possibly/likely serving some useful purpose--
ie, worth preserving possibly or worth intervening in to direct toward more ideal balances
(As opposed to simply cleansing/sterilizing as far as possible).

 

[janus]

Perhaps the most important finding here is cholate and deoxycholate, both of which are released by the liver/gallbladder to stimulate fat absorption. Since these metabolites transiently (but powerfully) stimulate serotonin synthesis, it may provide yet another explanation why Peat tries to steer away from fat, and why high fat diets are carcinogenic. I wonder if there is a study that compares the effects of different types of fat on cholate release. It would be a major win for Peat if PUFA stimulates a lot more cholate release than MUFA and saturated fat.

I wonder how the effects of these bile acids differ from those of the conjugated bile acids (i.e. glycine and taurine salts).

I'd also think that a continuously high bile flow would keep bowel transit time low and reduce serotonin synthesis, so maybe that's a difference from injecting preformed bile acids.

 

[haidut]

Perhaps the most important finding here is cholate and deoxycholate, both of which are released by the liver/gallbladder to stimulate fat absorption. Since these metabolites transiently (but powerfully) stimulate serotonin synthesis, it may provide yet another explanation why Peat tries to steer away from fat, and why high fat diets are carcinogenic. I wonder if there is a study that compares the effects of different types of fat on cholate release. It would be a major win for Peat if PUFA stimulates a lot more cholate release than MUFA and saturated fat.

I wonder how the effects of these bile acids differ from those of the conjugated bile acids (i.e. glycine and taurine salts).

I'd also think that a continuously high bile flow would keep bowel transit time low and reduce serotonin synthesis, so maybe that's a difference from injecting preformed bile acids.

Ironically, the germ-free rats in the study had a much longer bowel transit time. The scientists used bowel transit time to measure the effects of restoring "normal" serotonin levels by re-infecting the rats with bacteria, and the transit time shortened due to the increased serotonin. So, it seems that there is an optimal transit time probably controlled by serotonin. I wonder if low serotonin means constipation, how does Peat view that side effect and what can be done to remediate it. I guess he will say eat more carrot...

 

[tara]

I wonder if low serotonin means constipation, how does Peat view that side effect and what can be done to remediate it. I guess he will say eat more carrot...

Cascara sagrada?

 

[janus]

Ironically, the germ-free rats in the study had a much longer bowel transit time. The scientists used bowel transit time to measure the effects of restoring "normal" serotonin levels by re-infecting the rats with bacteria, and the transit time shortened due to the increased serotonin. So, it seems that there is an optimal transit time probably controlled by serotonin. I wonder if low serotonin means constipation, how does Peat view that side effect and what can be done to remediate it. I guess he will say eat more carrot...

Well, yeah, if the digestion has been characterized by overstimulation of the intestines and reliance on large amounts of serotonin, it could take awhile for the GI tract to regain sensitivity and require only low amounts of serotonin for proper function.

But we've seen that this applies to all metabolic processes.

If a constipated individual suddenly starts digesting built-up junk in the intestine and colon (as by injecting bile acids), you might expect that bacterial activity might first spike and then decline once the GI tract became relatively clean.

I came across some material that suggests antimicrobial properties of cholate. So maybe some metabolites have specific effects.

 

[tomisonbottom]

Ironically, the germ-free rats in the study had a much longer bowel transit time. The scientists used bowel transit time to measure the effects of restoring "normal" serotonin levels by re-infecting the rats with bacteria, and the transit time shortened due to the increased serotonin. So, it seems that there is an optimal transit time probably controlled by serotonin. I wonder if low serotonin means constipation, how does Peat view that side effect and what can be done to remediate it. I guess he will say eat more carrot...

Well, yeah, if the digestion has been characterized by overstimulation of the intestines and reliance on large amounts of serotonin, it could take awhile for the GI tract to regain sensitivity and require only low amounts of serotonin for proper function.

But we've seen that this applies to all metabolic processes.

If a constipated individual suddenly starts digesting built-up junk in the intestine and colon (as by injecting bile acids), you might expect that bacterial activity might first spike and then decline once the GI tract became relatively clean.

I came across some material that suggests antimicrobial properties of cholate. So maybe some metabolites have specific effects.

How would one "inject bile acids"?
I've tried taken bile supplements because I'm not digesting very well at all, but that just made me feel even more bloated. But is that what you're talking about?

 

[janus]

How would one "inject bile acids"?
I've tried taken bile supplements because I'm not digesting very well at all, but that just made me feel even more bloated. But is that what you're talking about?

See the mouse study quoted by haidut.

 

[Kasper]

I find these ideas of making your gut sterile kind of scary.

I've heard plenty of stories of people that tell antibiotics ruined their digestion, having diarrhea the rest of their life etc.

Colonizing the gut with non serotonin producing bacteria, seems more attractive to me

 

[cantstoppeating]

I find these ideas of making your gut sterile kind of scary.

I've heard plenty of stories of people that tell antibiotics ruined their digestion, having diarrhea the rest of their life etc.

Colonizing the gut with non serotonin producing bacteria, seems more attractive to me

How many of these people continue to eat pizza, burgers, gluten bread, PUFA laden fried foods and other non-Peat-non-metabolism foods?

Sterilising the gut with antibiotics and continuing to eat Peat friendly foods with daily carrots is the best thing you can do for yourself and you won't reap the benefits until you do it.

 

[javacody]

I wanted to address a few issues in this thread.

1. Gut bacteria are normal for us. Our microbiome is first populated when we leave the womb from the bacteria in and around our mother's vagina. Then, we likely get many more bacteria while we are breastfeed. Also, if any of you have kids, or have been around babies, you realize they put everything in their mouths. I wonder if this isn't part of the evolution of our microbiome?
2. Bacteria are stored in our appendix to repopulate our colon after sickness, diarrhea, etc. etc.

We are MEANT to have bacteria inside of us and on us. It's part of human evolution.

So I don't get where anyone would have the idea that having a sterile gut is a good thing. Even Ray says that the mice were fine, but they basically had no immune system.

Just an FYI, you kinda sorta need your immune system.

So, we have several questions we need to ask and have answered before we have a full understanding of this.

1. What is the OPTIMAL range of serotonin?
2. Which strains should we remove/add to achieve this target level?
3. What side effects would step 2 have (maybe good, maybe bad)?

Charcoal is interesting, because it will bind to all kinds of stuff. But it is at most a short term solution, right? It's the kind of thing you'll have to do for the rest of your life. Same with the carrot or bamboo shoots.

I think this is all Ray recommends (the above as generic solutions) because the science on our microbiome is still in its infancy. But I will bet you a million dollars that the answer isn't to wipe out all bacteria in our colons.

 

[pboy]

optimal serotonin is nill, I bet if they did a study they'd find dopamine stimulates GI as much as serotonin or more...definitely more. Ive been tracking everything for a long time, and that's a clear and obvious connection. Theres times id have a bout of fortune and/or an oppertunuity, a good interaction with people, something that really gets me going...tiems I made progress with other things...in the active flow of life moving quickly and decisive and it being fun, GI flows pretty fast and amazing. The times im sertonined out I feel more constipation potential.
Ive done expiriments that ...this is a really interesting topic to me and confirms some theories id come to myself, I had no science to define it but like...it goes deep man, probably people here wouldn't be able to vibe with me so I wont talk about it. Positivity and knowing...the kidna thing that makes any threat or fear somethign to laugh at, that level of always being good, is what you want. Anything that has to do with fear doubt restriction pain slowing down having to be patient...any kind of thing like that, hurts GI. Its about your mind in a huge way, and your spirit. You can be in a certain state, with certain thoughts, then witnessing something can (not eating anything, or changing anything else) profoundly change mood and flow and secretions, and its always something that gives hope and that a success is a real possibility. Bacteria, if that is what it is, are astringing, fear producing parasites basically, and what they spit isn't actually real. They poison via fear and doubt that leads to tensions, probably through the serotonin system. That translates into your mind of thoughts of fear and doubt basically, which greatly inhibit your action, and generally puts you in a less love inspiring mood to be around other people....hurting or stalling relationships. It also promotes thoughts of...wanting to help your threats or suddenly be ok with them, rather than seeing them for what you know and have felt they are, a problem. Take this all to its logical endpoint and you'll understand

 

[Amazoniac]

probably people here wouldn't be able to vibe with me so I wont talk about it.

Do it regardless, maybe someone will vibe with it..

 

[cantstoppeating]

I wanted to address a few issues in this thread.

1. Gut bacteria are normal for us. Our microbiome is first populated when we leave the womb from the bacteria in and around our mother's vagina. Then, we likely get many more bacteria while we are breastfeed. Also, if any of you have kids, or have been around babies, you realize they put everything in their mouths. I wonder if this isn't part of the evolution of our microbiome?
2. Bacteria are stored in our appendix to repopulate our colon after sickness, diarrhea, etc. etc.

We are MEANT to have bacteria inside of us and on us. It's part of human evolution.

So I don't get where anyone would have the idea that having a sterile gut is a good thing. Even Ray says that the mice were fine, but they basically had no immune system.

Just an FYI, you kinda sorta need your immune system.

So, we have several questions we need to ask and have answered before we have a full understanding of this.

1. What is the OPTIMAL range of serotonin?
2. Which strains should we remove/add to achieve this target level?
3. What side effects would step 2 have (maybe good, maybe bad)?

Charcoal is interesting, because it will bind to all kinds of stuff. But it is at most a short term solution, right? It's the kind of thing you'll have to do for the rest of your life. Same with the carrot or bamboo shoots.

I think this is all Ray recommends (the above as generic solutions) because the science on our microbiome is still in its infancy. But I will bet you a million dollars that the answer isn't to wipe out all bacteria in our colons.

This is a very recursive and common point of view.

Evolution happens through adaptation to the environment. We evolved through an environment that produced a bacterial filled gut but that doesn't mean a different environment, like a sterile gut, wouldn't be beneficial. Looking at evolution to see what's 'optimal' is like looking backwards while trying to move forward. All you'll see are previous environments while missing the possibility of creating a new environment that is orders of magnitude more beneficial to us.

 

[haidut]

I wanted to address a few issues in this thread.

1. Gut bacteria are normal for us. Our microbiome is first populated when we leave the womb from the bacteria in and around our mother's vagina. Then, we likely get many more bacteria while we are breastfeed. Also, if any of you have kids, or have been around babies, you realize they put everything in their mouths. I wonder if this isn't part of the evolution of our microbiome?
2. Bacteria are stored in our appendix to repopulate our colon after sickness, diarrhea, etc. etc.

We are MEANT to have bacteria inside of us and on us. It's part of human evolution.

So I don't get where anyone would have the idea that having a sterile gut is a good thing. Even Ray says that the mice were fine, but they basically had no immune system.

Just an FYI, you kinda sorta need your immune system.

So, we have several questions we need to ask and have answered before we have a full understanding of this.

1. What is the OPTIMAL range of serotonin?
2. Which strains should we remove/add to achieve this target level?
3. What side effects would step 2 have (maybe good, maybe bad)?

Charcoal is interesting, because it will bind to all kinds of stuff. But it is at most a short term solution, right? It's the kind of thing you'll have to do for the rest of your life. Same with the carrot or bamboo shoots.

I think this is all Ray recommends (the above as generic solutions) because the science on our microbiome is still in its infancy. But I will bet you a million dollars that the answer isn't to wipe out all bacteria in our colons.

This is a very recursive and common point of view.

Evolution happens through adaptation to the environment. We evolved through an environment that produced a bacterial filled gut but that doesn't mean a different environment, like a sterile gut, wouldn't be beneficial. Looking at evolution to see what's 'optimal' is like looking backwards while trying to move forward. All you'll see are previous environments while missing the possibility of creating a new environment that is orders of magnitude more beneficial to us.

Yep, we evolved with methods for survival and serotonin seems to be one of them. In times of struggle the organism slows down its metabolism to conserve resources, and serotonin is one of the primary mediators of this slow metabolism. This is the whole point in Selye's and Peat's arguments that constant state of survival is not healthy. The "optimal" level of serotonin is the one which promotes maximum metabolism since we assume we don't need any more the levels of serotonin needed for survival in tough times. So, the lower the serotonin the higher the metabolism and this implies you want serotonin to be as low as possible (yes, not zero). Serotonin has a very minimal physiological role and it has to do mainly with blood coagulation. Mice with germ-free guts still produce enough serotonin to fulfill that role so having a germ-free gut has been shown at least in rodents to confer superior health and longevity without causing bleeding disorders.
I don't think Peat is against being germ-free, he just said it's not practical since the gut will eventually get colonized by eating germy food that even stomach acid cannot kill completely. However, presumably there may be people out there with the resources and/or motivation to pull this off in a (expensive) sterile environment.
Finally, animals with germ-free guts have superb immune system and are very resilient to both infection and "autoimmune" diseases. The closest modulator of the immune system that mimics germ-free gut is niacinamide. Peat has said ( and I have confirmed through studies) that it both boosts the immune system and protects against autoimmunity. Unsurprisingly, in high doses of 4g - 8g niacinamide is potently antiserotonergic as shown by the old study from 1950s I posted long time ago on the forum. So, not sure how the microbiome is beneficial for the immune system given its mandatory role for serotonin production, with serotonin being one of the most potent immune suppressors out there.
Just my 2c.

 

[Vinero]

Interesting how substances that lower serotonin also boost the immune system. In particular Theanine, Niacinamide, Zinc, BCAA etc. Seems like serotonin is a suppressor of the immune system.

 

[haidut]

Interesting how substances that lower serotonin also boost the immune system. In particular Theanine, Niacinamide, Zinc, BCAA etc. Seems like serotonin is a suppressor of the immune system.

Yes, it is. Serotonin is extremely catabolic through its stimulation of ACTH and cortisol. That's why cyroheptadine lowers cortisol - by blocking serotonin. Anything that boosts cortisol will suppress the immune system, and as such the serotonin connection should make perfect sense.
Bromocriptine and other dopaminergic drugs are being tried in diseases like HIV due to their antiserotonergic effect. The Wiki page says bromocriptine is approved for treating type II diabetes but of course the proposed mechanism of action is "unknown" to mainstream medicine.
Bromocriptine - Wikipedia, the free encyclopedia

No medical official or pharma exec wants to admit that serotonin destroys oxidative metabolism by directly stimulating glycolysis, and suppresses the immune system (either through cortisol or directly) and thus contributes to cancer and diabetes. Peat wrote that the 3 poisonous amines ammonia, histamine, and serotonin are best kept as low as possible.

 

[TeslaFan]

I read this interesting Soviet research from the 60s on antibiotics-serotonin relationship:

http://link.springer.com/article/10.100 ... 914#page-1

 

[javacody]

I wanted to address a few issues in this thread.

1. Gut bacteria are normal for us. Our microbiome is first populated when we leave the womb from the bacteria in and around our mother's vagina. Then, we likely get many more bacteria while we are breastfeed. Also, if any of you have kids, or have been around babies, you realize they put everything in their mouths. I wonder if this isn't part of the evolution of our microbiome?
2. Bacteria are stored in our appendix to repopulate our colon after sickness, diarrhea, etc. etc.

We are MEANT to have bacteria inside of us and on us. It's part of human evolution.

So I don't get where anyone would have the idea that having a sterile gut is a good thing. Even Ray says that the mice were fine, but they basically had no immune system.

Just an FYI, you kinda sorta need your immune system.

So, we have several questions we need to ask and have answered before we have a full understanding of this.

1. What is the OPTIMAL range of serotonin?
2. Which strains should we remove/add to achieve this target level?
3. What side effects would step 2 have (maybe good, maybe bad)?

Charcoal is interesting, because it will bind to all kinds of stuff. But it is at most a short term solution, right? It's the kind of thing you'll have to do for the rest of your life. Same with the carrot or bamboo shoots.

I think this is all Ray recommends (the above as generic solutions) because the science on our microbiome is still in its infancy. But I will bet you a million dollars that the answer isn't to wipe out all bacteria in our colons.

This is a very recursive and common point of view.

Evolution happens through adaptation to the environment. We evolved through an environment that produced a bacterial filled gut but that doesn't mean a different environment, like a sterile gut, wouldn't be beneficial. Looking at evolution to see what's 'optimal' is like looking backwards while trying to move forward. All you'll see are previous environments while missing the possibility of creating a new environment that is orders of magnitude more beneficial to us.

Yep, we evolved with methods for survival and serotonin seems to be one of them. In times of struggle the organism slows down its metabolism to conserve resources, and serotonin is one of the primary mediators of this slow metabolism. This is the whole point in Selye's and Peat's arguments that constant state of survival is not healthy. The "optimal" level of serotonin is the one which promotes maximum metabolism since we assume we don't need any more the levels of serotonin needed for survival in tough times. So, the lower the serotonin the higher the metabolism and this implies you want serotonin to be as low as possible (yes, not zero). Serotonin has a very minimal physiological role and it has to do mainly with blood coagulation. Mice with germ-free guts still produce enough serotonin to fulfill that role so having a germ-free gut has been shown at least in rodents to confer superior health and longevity without causing bleeding disorders.
I don't think Peat is against being germ-free, he just said it's not practical since the gut will eventually get colonized by eating germy food that even stomach acid cannot kill completely. However, presumably there may be people out there with the resources and/or motivation to pull this off in a (expensive) sterile environment.
Finally, animals with germ-free guts have superb immune system and are very resilient to both infection and "autoimmune" diseases. The closest modulator of the immune system that mimics germ-free gut is niacinamide. Peat has said ( and I have confirmed through studies) that it both boosts the immune system and protects against autoimmunity. Unsurprisingly, in high doses of 4g - 8g niacinamide is potently antiserotonergic as shown by the old study from 1950s I posted long time ago on the forum. So, not sure how the microbiome is beneficial for the immune system given its mandatory role for serotonin production, with serotonin being one of the most potent immune suppressors out there.
Just my 2c.

I've actually heard Ray in an interview say that germ free mice had immune systems that were lacking, and there is science to support this.

http://www.nature.com/news/early-exposure-to-germs-has-lasting-benefits-1.10294

 

[pboy]

that's like saying you want to have a roommate whose a piece of crap because it will help build your immunity for the people you have to deal with at work. The pursuit should always be clean gut, and if threats appear along the way deal with it as they come, don't purposefully add more a burden. Theres something strange about this gut bacteria thing....so many people are clinging to the notion that its beneficial...in a beyond normal way, it must be their gut bacteria talking

 

[Zachs]

I think people keep hearing sterile gut and thinking our intestines are make from stainless steel and we just need to wipe it clean.

Having a sterile gut is impossible and we would most likely die quickly without any gut bacteria. The main points are to keep the bacteria from traveling up the gut where they cause trouble with normal digestion and to keep them in check and not let them proliferate out of control.