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Serotonin and the gut/brain

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ForecasterJason
ForecasterJason Posts: 2,577 Member
in Debate Club
I'm opening a discussion on tryptophan and serotonin and their production/impacts for the gut and brain. I've heard that while most serotonin is produced in the gut, it cannot cross the blood/brain barrier and so it does not impact serotonin in the brain. I've also heard the reverse, that reduced serotonin production in the gut impacts serotonin production in the brain, and that there is a gut/brain axis. I know that serotonin is produced from tryptophan. From my understanding, and I'm not sure if this is totally correct, but this serotonin is produced in the gut. The brain is then able to access some of this serotonin.

I've also read that when gut inflammation exists (from food sensitivities, infections, stress, etc.), tryptophan cannot get converted properly to serotonin (which, according to the sequence mentioned above, would impact brain serotonin levels as well).

Basically, what I'm wondering is if you guys think there is truth to the idea that any issues in the gut can potentially directly impact brain serotonin levels. I can't find it now, but I know there was a post in some other thread here that claimed probiotics are totally unrelated to brain disorders because gut serotonin cannot cross the blood-brain barrier. But I've also seen other sources (granted I'm not referring to peer-reviewed ones) that say gut issues can directly impact the brain, and there seems to be some scientific explanation behind it.

Replies

  • auddii
    auddii Posts: 15,357 Member
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    A somewhat recent review (http://www.sciencedirect.com.ezproxyhost.library.tmc.edu/science/article/pii/S0092867415003530) entitled "Gut microbiota: the link to your second brain" discussed that microbiota can increase serotonin, which in turn affects many different physiological processes (one of the major functions of serotonin is regulating GI motility, . However, it does not describe any change in brain levels of seretonin or any mental affect at all.

    I could see the argument that increased inflammation of the gut could reduce GI motility and lead to further GI problems, but I have not seen any literature that it in any way directly affects the brain.
  • senecarr
    senecarr Posts: 5,377 Member
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    The general consensus of evidence is
    Serotonin cannot pass the blood brain barrier, therefore direct exchange between CNS use and intestinal use isn't happening.
    Tryptophan is used to synthesize serotonin and tryptophan can cross the blood brain barrier.
    However, tryptophan in food likely does not increase serotonin CNS availability because it must compete for transport with other amino acids found in food.
  • ForecasterJason
    ForecasterJason Posts: 2,577 Member
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    Ok. Is it reasonable to say though that brain serotonin can influence GI motility?
  • senecarr
    senecarr Posts: 5,377 Member
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    ForecasterJason wrote: »
    Ok. Is it reasonable to say though that brain serotonin can influence GI motility?

    Directly? Seems unlikely that any direct chemical transmission happens.
    Indirectly, serotonin levels tend to reflect and probably even influence certain mental states. These in turn influence a number of other physiological processes including digestion. For example, people with certain anxieties or panic disorders might be put on SSRI's to increase serotonin in the CNS, and relieve the symptoms. One result of this would probably be that the GI tract slows down, since anxious or panic prone individuals tend to end up with various forms of GI upset and fast GI clearing.
  • ForecasterJason
    ForecasterJason Posts: 2,577 Member
    edited March 2016
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    senecarr wrote: »
    ForecasterJason wrote: »
    Ok. Is it reasonable to say though that brain serotonin can influence GI motility?

    Directly? Seems unlikely that any direct chemical transmission happens.
    Indirectly, serotonin levels tend to reflect and probably even influence certain mental states. These in turn influence a number of other physiological processes including digestion. For example, people with certain anxieties or panic disorders might be put on SSRI's to increase serotonin in the CNS, and relieve the symptoms. One result of this would probably be that the GI tract slows down, since anxious or panic prone individuals tend to end up with various forms of GI upset and fast GI clearing.
    Alright, thanks for the explanation.

    According to this website, gut inflammation causes an increase in an enzyme called IDO. "But IDO is also important because it degrades tryptophan, the precursor of serotonin and serotonin’s metabolite, melatonin, to kynurenine. The more tryptophan shuttled to the kynurenine pathway, the less is available for the production of serotonin or melatonin." It also notes, "Instead, tryptophan is converted to kynurenine, which increases the production of both 3-hydroxy-kynurenine (3-OH-KYN) and quinolinic acid (QUIN), both of which easily cross the blood-brain barrier."

    From what this saying, gut inflammation causes a reduced amount of tryptophan available to travel from the gut to the brain. This would mean that the amount of serotonin available to be produced by the brain would be lower. In addition, the door becomes open for eventual brain-related disorders.

    Do you agree with what the article is saying in that regard?

    Edit: In relation to your previous post that tryptophan in food may not increase serotonin availability for the brain, I'm confused, as I thought that was how serotonin does get produced there. Or are you saying an increase above dietary needs would not increase tryptophan availability there due to the other amino acids trying to be transported?
  • ForecasterJason
    ForecasterJason Posts: 2,577 Member
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    Another thing: Factors such as sunlight and exercise are known to raise brain serotonin levels. Is tryptophan involved in this, or do these factors just raise serotonin independent of the tryptophan>HTP>serotonin pathway?
  • senecarr
    senecarr Posts: 5,377 Member
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    ForecasterJason wrote: »
    senecarr wrote: »
    ForecasterJason wrote: »
    Ok. Is it reasonable to say though that brain serotonin can influence GI motility?

    Directly? Seems unlikely that any direct chemical transmission happens.
    Indirectly, serotonin levels tend to reflect and probably even influence certain mental states. These in turn influence a number of other physiological processes including digestion. For example, people with certain anxieties or panic disorders might be put on SSRI's to increase serotonin in the CNS, and relieve the symptoms. One result of this would probably be that the GI tract slows down, since anxious or panic prone individuals tend to end up with various forms of GI upset and fast GI clearing.
    Alright, thanks for the explanation.

    According to this website, gut inflammation causes an increase in an enzyme called IDO. "But IDO is also important because it degrades tryptophan, the precursor of serotonin and serotonin’s metabolite, melatonin, to kynurenine. The more tryptophan shuttled to the kynurenine pathway, the less is available for the production of serotonin or melatonin." It also notes, "Instead, tryptophan is converted to kynurenine, which increases the production of both 3-hydroxy-kynurenine (3-OH-KYN) and quinolinic acid (QUIN), both of which easily cross the blood-brain barrier."

    From what this saying, gut inflammation causes a reduced amount of tryptophan available to travel from the gut to the brain. This would mean that the amount of serotonin available to be produced by the brain would be lower. In addition, the door becomes open for eventual brain-related disorders.

    Do you agree with what the article is saying in that regard?

    Edit: In relation to your previous post that tryptophan in food may not increase serotonin availability for the brain, I'm confused, as I thought that was how serotonin does get produced there. Or are you saying an increase above dietary needs would not increase tryptophan availability there due to the other amino acids trying to be transported?

    Now that kind of effect would be a plausible mechanism rather than the intestines and brains directly exchanging serotonin, though I'd have to crawl some PubMed for how established this pathway is. I'd admit upfront, I tend to be skeptical of things that tend to view depression (which looks like it can be caused by lack of serotonin) as a form of inflammation. I'm actually biased in general against inflammation hypotheses from the onset because it has become a bit of a woo buzzword. So it is something I'd need to look into deeper. I'll tag the thread in case anyone else has anything interesting in the interim.
  • TheLittleFangs
    TheLittleFangs Posts: 205 Member
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    This was an incredibly interesting thread and I thank all contributors.

    I have inflammatory bowel. The SSRIs I've taken a significant amount actually caused ulceration and scarring on my gut. Even simulated levels I was unable to uptake. Sertraline and the SNRI Duloxetine were the most affective in mental health capacity but eventually I had to quit due to the affect on my gut health.

    I suffer too from Fibromyalgia and am being investigated for Rheumatoid arthritis. I have hypothyroidism and inflammation I'd a part of my life. With all of these come rampant insomnia.

    I'd love to hand myself over to be studied as I'd love to know the answer to the above. I'm now reading through the links etc

    Thank you
  • alasin1derland
    alasin1derland Posts: 575 Member
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    I remember researching serotonin blood barrier a couple years ago and I remember there was a link to melatonin so I googled that. The paragraph titled the tryptophan pathway on page 323 discusses this and continues on page 324. Its just a short excerpt from the book.
    https://books.google.ca/books?id=cKZfBQAAQBAJ&pg=PA324&lpg=PA324&dq
  • ForecasterJason
    ForecasterJason Posts: 2,577 Member
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    alasin1derland, that's a good resource.

    Interestingly, it seems like the conversion of tryptophan being degraded to kynurenine synthesis is not always a bad thing, according to this source on tryptophan.

    I also find it interesting that according to this article, exercise can shuttle more tryptophan into the brain, but yet sunlight can increase serotonin even with depletion of tryptophan.

    So, it sounds to me like increasing serotonin through exercise (and maybe some other methods as well) relies on diet, while increasing serotonin through sunlight exposure can occur independent of diet. Also, I would think it can be concluded that in most healthy individuals, the presence of adequate dietary tryptophan and absence of notable gut inflammation are the main methods that allow for sufficient serotonin production in the brain. Spending time in the sun would boost serotonin even more.

    Based on my personal experience, as I think about this makes sense. I find that sunlight exposure (especially mostly cloud-free days and combined with exercise I enjoy) gives me a substantial boost in mood (which can most likely be at least somewhat attributed to serotonin). However, exercise on its own does not have as much of an effect.
  • jgnatca
    jgnatca Posts: 14,464 Member
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    How about the interaction between capsaicin and serotonin?
  • ForecasterJason
    ForecasterJason Posts: 2,577 Member
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    Bumping to see if there is additional input on the subject
  • lithezebra
    lithezebra Posts: 3,670 Member
    edited March 2016
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    Why would serotonin produced in the gut need to cross the BBB for gut issues to affect the brain? Here's an abstract for an article that suggests several routes by which gut microbiota might interact with the brain. Unfortunately the article is behind a pay wall, unless your library subscribes to Nature, as mine does.
    http://www.nature.com/nrn/journal/v13/n10/full/nrn3346.html
  • ForecasterJason
    ForecasterJason Posts: 2,577 Member
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    I found another article that explains the pathways that tryptophan can take. So with regards to interaction with the gut, it seems to me that this is how it all works. Even if the cofactors needed for the tryptophan>serotonin conversion in the brain are present, gut inflammation can override that and degrade tryptophan to kynurenine and/or quinolinic acid.

    http://lidtke.com/the-lidtke-letter-why-dont-your-supplements-work/
  • jgnatca
    jgnatca Posts: 14,464 Member
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    Gadgets like this may help work out these interactions.

    http://www.engineering.com/DesignerEdge/DesignerEdgeArticles/ArticleID/6769/Harvard-Scientists-Create-Organs-on-a-Chip.aspx

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