Tyramine Intolerance and The Gut, Part I: The Microbiome

Tyramine intolerance, like most food sensitivities, probably involves something going wrong in the gut (microbiome). But what is the microbiome, and what goes wrong that causes this? The Rogue Scientist explores in this multi-part series.

Why do people develop food sensitivity, including tyramine and histamine intolerance?

The short answer is we don’t really know. However, we do have a few educated guesses.

For example, genetics. If you inherited a slow-acting gene variant for, say, the monoamine oxidase enzyme that breaks down tyramine, you may have a more difficult time metabolizing tyramine, so it builds up in your system.

However, I believe there’s far more to the story. For one, our genes don’t change. But most people with tyramine intolerance developed it in middle age, which means something else changed.

Which leads me to another—and, in my opinion, more intriguing—educated guess:

Tyramine intolerance develops because something goes awry in the gut.

So, of course, I set out to write an article on this topic, maybe learn a few things. It didn’t take long before I hit a roadblock—this topic, i.e. the gut, is far too complex to encompass in one article.

By the way, this happens to me a lot, a “simple” topic blowing up to something much larger. You’d think I’d known better, right? This is science, after all, where nothing’s simple.

Anyway, this will begin a series of articles addressing the gut (or microbiome) and how it may play a role in tyramine intolerance.

This article will begin with the fundamentals: What is the microbiome? What does it do? And how can it possible influence tyramine intolerance, or any food intolerance?

What is the Microbiome?

According to the National Human Genome Research Institute:

The microbiome is a term used to describe the specific collection of microorganisms (such as fungi, bacteria and viruses) that exist in a particular environment. The word is often used to describe the community of microorganisms that live in or on the human body (e.g., in the stomach or on the skin). One human has about 40 trillion bacteria and other microbes in their system.

These microorganisms (microbiota) live in three key places: the skin, the vagina, and the digestive canal that stretches from your mouth to your anus. This series will focus on the latter, since the digestive portion of the microbiome is most likely related to food intolerance.

These microbiota—bacteria, fungi, and viruses—are crucial for our ability to function. We literally cannot live without them.

Science has begun to recognize that a healthy gut leads to good health, and more research funds have been funneled to study the microbiome. Likewise, as anyone who’s ever had IBS or the stomach flu can tell you, a problem in the gut can lead to serious health problems.

What Do Microbiota Do?

Why do we need these microbiota? What do they do?

They help with several important functions, including metabolism of nutrients, absorption of minerals, digesting foods we cannot (e.g. fiber), maintaining the structural integrity of the gut mucosal barrier, aiding with immunity, and protecting against pathogens.

What factors impact gut microbiota? Common factors include how you were birthed (vaginal or caesarian), diet (including diet during infancy, such as breast milk vs. formula), stress, and antibiotic use. Other factors can include the sterility of a child’s environment, and (interestingly) whether you have pets in the home.

Microbiome and Disease

Gut microbiota have been associated with many human diseases, including inflammatory bowel diseases and irritable bowel syndrome, obesity, diabetes, and mental disorders.

The mucosal barrier that lines the intestinal tract is important for health as well. Its job is to allow nutrients across the barrier and into the body while blocking harmful organisms or substances. In disease, this barrier gets disrupted, either as a cause or consequence of disease.

Stress can also weaken the mucosal barrier.

Research has shown that many chronic diseases, including diabetes, eczema, coeliac disease, bowel disease, and others are linked to lower diversity of bacterial microbiota. To combat this, science has begun experimenting with fecal transplant—yes, taking feces from a healthy individual and transferring it to someone with a specific disease—and, lo and behold, the new feces and the microbiota it contains can improve the afflicted person’s health.

Seriously, who would have ever guessed human poop would become something valuable??

Microbiota Make Neurotransmitters, and Other Fascinating Facts

I’ve listened to several podcasts discussing gut function and health, all run by experts. Two that stand out come from Dr. Andrew Huberman’s podcast: one where he taught listeners all about the gut and its relationship with the brain, and another where he interviewed gut expert Dr. Justin Sonnenburg. Here are a few key things I learned:

  • Your gut microbiota have their own genes, which can make enzymes that help us break down foods.
  • What you eat can change the enzymes the microbiota make.
  • There’s both a direct and indirect relationship between your gut microbiota and what happens in your brain. In fact, we have neurons in our gut!
  • Your microbiota play a direct role in immunity. Believe it or not, a large portion (like 70%) of your immune system resides IN YOUR GUT.
  • Microbiota can make neurotransmitters, and different species make specific neurotransmitters. (In fact, most serotonin, something we associate with the brain and behavior, is made in the gut.)
  • When the gut microbiota breaks down dietary fiber, it produces important molecules (e.g., short-chain fatty acids) with benefits that go beyond the gut.

What Does All This Have to Do with Tyramine Intolerance?

When you take the information above, which is only the very tippy-top of a huge iceberg, you can begin to see where gut function (or disfunction) can play a role in tyramine intolerance.

For example:

  • If your gut microbiota have their own genes that make enzymes to help us break down foods, it makes sense that if we don’t have enough of a given species, certain foods (e.g. high-tyramine foods) might not get broken down properly.
  • If there’s a relationship between your gut microbiota and your brain activity, it’s possible that could explain why eating certain foods (tyramine included) can have a strong impact on your mood and behavior.
  • If microbiota can make neurotransmitters, and different species make specific neurotransmitters, then what if people with tyramine intolerance have too many of the bacteria that make norepinephrine (the neurotransmitter that causes all those unpleasant symptoms), or not enough of the bacteria that make calming GABA?
  • MAO-A, the enzyme that breaks down tyramine, does its job in the gut. Even if you have a slow-acting variant of MAO-A, something changed between youth and middle age that caused the enzyme to quit working as well. Possibly something in the gut, such as:
  • Gut microbiota impact how genes behave (whether a gene gets expressed or silenced, and when.) So if MAO-A stops working properly, the reason could have to do with the gut microbiota.

These are merely educated guesses, of course. But it’s fair to say that when it comes to tyramine and other food intolerance, the gut is where it’s at.

If you want more information about tyramine intolerance and how to deal with it, check out The Tyramine Intolerance Handbook.

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Related Articles

Tyramine Intolerance and The Gut, Part II: Probiotics

Tyramine Intolerance and The Gut III: Neurotransmitters

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The Rogue Scientist

Christie Hartman is a writer and scientist specializing in science-based health. A biology major as an undergrad, she completed her PhD in behavioral genetics at the University of Colorado Boulder. Before starting her writing career, she worked as a scientist and professor at CU’s School of Medicine, where she studied the genetic contributions to substance abuse and antisocial behavior.

9 thoughts on “Tyramine Intolerance and The Gut, Part I: The Microbiome”

  1. So I listened to most of this video. He is encouraging increasing intake of fermented foods, however I have read fermented foods are high in tyramine which brings on migraine. Confused.

  2. My favourite hypothesis is that adult-onset tyramine sensitivity is due to splice variants; the ratio of them may alter as we age.
    Apparently some genes have hundreds of splice variants.
    There’s an example in fruit fly, some gene that has more splice variants detectable as expressed than the total number of genes in the fly.

  3. From that 2021 paper about amines and gut microbiota :
    “Tryptamine in the gastrointestinal tract can induce serotonin secretion by enterochromaffin cells, which are important for gastrointestinal motility.”

    Well, there’s certainly been a strong suggestion of tryptamine hallucinations in many of my episodes.
    This caught my eye though because peristalsis itself often seemed to stop as the headache built up force.
    It was a remarkable.

  4. Hi, I got interested in your articles when I tried to understand tyramine. Based on my food journal I realize I’m sensitive to aged, cured and fermented foods. Many of those tyramine rich foods include msg, so maybe msg unnecessarily gets a bad rap.
    The tyramine side effect for me is staying wide awake at night as it could be due to excess norepinephrine. If I take Benadryl, I fall asleep. I assume the anti-histamine quells the norepinephrine.
    My question to you is have any studies been done on the impact of estrogen on tyramine? My sensitivity started only after menopause. Does lack of estrogen prevent the body from modulating tyramine?

    1. I wish I knew the answer to your question! I know so many women who start getting food intolerances, or their existing intolerances worsen a year or two into menopause. Myself included.

  5. “Gut microbiota impact how genes behave (whether a gene gets expressed or silenced, and when.) So if MAO-A stops working properly, the reason could have to do with the gut microbiota.”

    It’s very possible that a diet that chronically lacks fiber can cause long-term deficits in SCFAs. Since SCFAs are all potent HDAC inhibitors, a deficiency in both acetate and subsequent overexpression of HDAC can put important genes like MAO-A in a hyper-methylated state.

    If someone is a genetic low producer of MAO-A, a lack of SCFA would cause that enzyme to be even more suppressed. If that’s the case then the person needs to find a high-fiber diet that doesn’t contain contain trigger foods. Just a theory.

  6. Yes, this makes a lot of sense, I had a similar theory too. I am having a 6+ month IBS flare that keeps me in a permanent bloated state and during the worst periods, it was causing lots of reflux which resulted in unpleasant Dyspnea. Now I am dealing mainly with the constant discomfort and insomnia. I can see that tyramine high foods lead to insomnia and other symptoms, but what didn’t make sense is why now. Why has my body become this sensitive to it, and this article reaffirmed my theory. I’ve been looking into gut-directed hypnotherapy (Nerva) and hopefully that resolves the IBS flare, and hopefully that also resolves my hypersensitivity to tyramine.

    It might also be useful for people to check out Dr. K’s mini-lecture on Trauma. Most people actually have trauma (and he confirms this as well) and it’s a good predictor of IBS development.

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