The Gut Microbiome or How Your Gut Controls Your Mood


We all know what our gut is. It’s that weird place in our tummies that growls like a grumpy old man every time we’re hungry and every time we eat that bowl of bibimbap that was way too spicy for us, but that we ate anyway because we wanted to impress our friends. But what makes that delicious bibimbap turn into complete hellfire the next day?

Answer: The microbiota that inhabit it. Basically, your gut is a magical place chock-full of microorganisms which, well, live there. Just like you (maybe, I don’t know you really), they wake up, go to work, eat, have babies, sleep, poop, and have the occasional secret party. Nobody knows for sure how all of them got there in the first place, but there are many theories in place. These tiny fellows, it is believed, are partly inherited (from your mom, through birth and breastmilk), and partly gained through exposure to your environment. In a sense, that time you ate that strawberry straight from the ground, you invited a few of these homies to live in your gut. And that’s a good thing. Research so far shows that a healthy gut is a diverse gut, meaning it contains all kinds of microorganisms, from all kinds of places. Sure, it’s good to wash your hands, but living in a very sterile environment can mean that you deprive yourself of that diversity, which can lead to a variety of medical conditions.

Just so you understand what is going on in your gut, think about this for a second: on average, the human gut contains about 100 trillion microbes, composed of bacteria, viruses, fungi, and other small critters we won’t be discussing here. It was believed that the ratio of microorganism cells to human cells in the human body was 10:1, but estimates vary. A recent one claimed it’s about the same, so a 1:1 ratio. Either way, that’s probably way more than you thought, right? “And”, you might be wondering, “what are these little bastards doing in my belly?”. Well, they mainly just help with breaking down nutrients into even more nutritious nutrients. They are involved in a process called fermentation, which you might have heard of if you ever read your kombucha bottle label. In a sense, they are producing the equivalent of a can of beer per day, to help support you and your immune system. They also help you get that sweet, sweet energy from the food you eat, through a process called “calorie extraction”.

So, why are we still talking about this? Shouldn’t we just go grab some ice-cream instead? But what flavor should we choose?

“Trust your gut”, your mom might tell you when she sees you’re really unsure which flavor ice-cream you want to get and you’ve been awkwardly standing there in front of the ice-cream display for an inhumane amount of time saying “umm” when you know, deep down, you really want the unicorn swirl. Well, your mom isn’t really wrong (she never is, is she?).

The gut and the brain

Do YOU decide that you need that delicious unicorn swirl? Does your mom? Or, did you trust your gut after all?

Until recently, we’ve been led to believe that “trust your gut” is not really about the gut. What about when you get “butterflies in your stomach” as you see that pretty girl walking towards you, or you are feeling particularly nauseous before that huge test that you completely forgot about? Well, as you might’ve sensed after reading the section headline, the gut actually communicates with the brain. Scientists have very cleverly named this connection “the gut-brain axis”. Imagine this axis as a big river that somehow, magically, flows both ways between the brain and the gut, with a lot of little rivers that feed into it. This main river would be the vagus nerve – a long nerve that connects the intestines to the brain stem and helps them send little messages in a bottle from one to another. The gut microbiota might say “Hey, man, we haven’t been fed in a while… Not cool.”, to which the brain stem replies, “Oh, okay, let me just pass that on for you”. The brain stem then tells its friend, the limbic system (which regulates our emotions), that the gut demands some nutritional sacrifice, to which your limbic system says “Alright, already! You crybabies! I’ll have to do something about that. *turns on the hyperventilation switch* There.”. Then what you might be feeling is distress, or a popular phenomenon called being “hangry” (a lovely combo of being both hungry and angry because of it). Then, your limbic system sends the following message in a bottle to your gut: “I might have overdone it, he’s hangry now. I repeat, he’s hangry!”. So now, your gut reacts to this whole new level of stress that you’re experiencing by making you poop uncontrollably.

To put it in more scientific terms, the gut-brain axis serves as a communication platform for the endocrine, immune, and autonomic nervous systems. The endocrine system produces the hormones you need to become hangry in the first place, but also to cool down from your intense breakdown, while the immune system helps you fight off the bad guys trying to break into your house (e.g. harmful organisms that want to take over your body) while you’re busy having said breakdown. And then, the autonomic nervous system comes in to just take over everything because, let’s face it, you’re a mess when you’re hungry.

The gut and mood

As we’ve discussed so far, the brain and the gut are in constant crosstalk. An important player in this back-and-forth conversation is the endocrine system, particularly involving a little something called the hypothalamic-pituitary-adrenal axis, or HPA. This axis is basically a connection between the hypothalamus, the pituitary, and the adrenal glands, a system put in places by our fabulous bodies to regulate response to stress, energy use, immune function, mood, and not to mention our libidos (wink wink). Evidence for this kind of link between the HPA and the microbiota comes from mice studies, where researchers found increased levels of hormones corticosterone and adrenocorticotropin in response to stressful situations in germ-free mice, as compared to conventional mice. These little hormones help us deal with stress, basically. What’s more, we know that stress increases intestinal permeability (meaning that it allows microorganisms such as our gut bacteria to sneakily pass through the gut walls and access immune cells and neuronal cells of the enteric nervous system, which is like a mesh of neurons that babysit the gut). All this sneaking around that the gut bacteria do allows them to have an open gateway to the central nervous system in your “head brain”, so that they can whisper insistently to you that you need to eat that whole sleeve of Oreos or else you’ll die of anxiety. What’s more interesting is how these tiny critters in your belly can actually induce stress through the vagus nerve, initiating this whole process, forcing those delicious Oreo cookies down your throat. The body reacts to stress by inducing inflammation (thanks, immune system!), and obviously the only way to manage that inflammation in your body is by trashing it with inflammation-causing foods, such as Oreos. But man, are they good!

So, you might be asking, what does that have to do with depression and anxiety? Well, our curious cat, we know that stress is one of the biggest factors involved in mood and anxiety disorders, and if your tiny gut buddies can easily access that stress trigger, they can probably induce some of that delicious melancholia. How do we know? Take some really sad mice and give them an antibiotic, or treat them with probotics, and see if they’re just as sad afterwards. Researchers have obviously tried these pill cocktails out and found that, indeed, these mice were “happier” (which is a bit of an overstatement because we can only look at how they behave). So, say we drop a sad mouse in a maze. That mouse is probably like “What’s the point, it’s not like it matters anyway, they’re just gonna add more levels later. Better just sit here and do nothing instead”. But give that mouse some sweet biome-altering meds, and you might see he’s all like “Yeah, challenge accepted, let’s explore!”. So, you see, these kinds of experiments show that the gut is quite involved in how we feel and act. There are obviously more factors at play, such as how the microbiota can modulate signaling systems in the central nervous system, but that’s a discussion for another time. We only hope that we have managed to motivate you to explore, be curious about, and discuss with your drinking buddies about the cross-talk between the gut, the endocrine (HPA), the immune, the autonomic (for involuntary responses), and the central nervous systems.

Would you like to know more? Check out these useful links, videos, and papers. And don’t forget to follow us on Instagram or Twitter to stay up-to-date with our most recent posts.

Sender, R., Fuchs, S., & Milo, R. (2016). Revised estimates for the number of human and bacteria cells in the body. PLoS biology14(8), e1002533.

Hsiao, W. W., Metz, C., Singh, D. P., & Roth, J. (2008). The microbes of the intestine: an introduction to their metabolic and signaling capabilities. Endocrinology and metabolism clinics of North America37(4), 857-871.

Valdes, A. M., Walter, J., Segal, E., & Spector, T. D. (2018). Role of the gut microbiota in nutrition and health. Bmj361.

Sudo, N., Chida, Y., Aiba, Y., Sonoda, J., Oyama, N., Yu, X. N., … & Koga, Y. (2004). Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice. The Journal of physiology558(1), 263-275.

Ait-Belgnaoui, A., Durand, H., Cartier, C., Chaumaz, G., Eutamene, H., Ferrier, L., … & Theodorou, V. (2012). Prevention of gut leakiness by a probiotic treatment leads to attenuated HPA response to an acute psychological stress in rats. Psychoneuroendocrinology37(11), 1885-1895.

Goehler, L. E., Park, S. M., Opitz, N., Lyte, M., & Gaykema, R. P. (2008). Campylobacter jejuni infection increases anxiety-like behavior in the holeboard: possible anatomical substrates for viscerosensory modulation of exploratory behavior. Brain, behavior, and immunity22(3), 354-366.

Lyte, M., Li, W., Opitz, N., Gaykema, R. P., & Goehler, L. E. (2006). Induction of anxiety-like behavior in mice during the initial stages of infection with the agent of murine colonic hyperplasia Citrobacter rodentiumPhysiology & behavior89(3), 350-357.

Foster, J. A., & Neufeld, K. A. M. (2013). Gut–brain axis: how the microbiome influences anxiety and depression. Trends in neurosciences36(5), 305-312.

The Brain-Gut Connection

The Simplified Guide to the Gut-Brain Axis – How the Gut and The Brain Talk to Each Other

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