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  • Selma Weerdenburg

The wonders of the collaboration between your microbiota and your brain

Updated: Feb 21

Do you ever wonder what the food you eat experiences when it travels through your gastrointestinal tract? Okay, probably not – after chewing it doesn't look so appetizing anymore and your food cannot see or feel anyway. However, your food is packed with millions, maybe even billions of microbes – and those are living organisms! They travel through your gastrointestinal tract (your gut) and – even though not all will survive the acidic environment of your stomach – some will reach your intestines. And what they encounter there is unimaginable…


With this blog post, I want to show you why it is so important that researchers once did wonder what these bacteria experience in your gut, and what they have discovered since.


The inside of your gut is filled with microbes! During your life, your gut has collected and selected this whole community of bacteria. Some researchers even think microbes started living in your gut before you were born! These tenants of your gut are called microbiota. Most of these microbes are continuously growing in your gut; they are commensals – meaning they live in your body without causing disease. They even help us in several ways! They all have specific jobs to maintain harmony in their residence and keep their landlord, you, happy. Together, all microbes in and on your body have an impressive genetic repertoire, forming a microbiome consisting of approximately 600,000 genes. To put things in perspective, that’s 26 times more than all the genes in your own genome. There are so many bacteria in your gut, that they outnumber the human cells!


Your microbiota, as well as their activity, are probably very different from mine. That is because the microbiota are affected by several factors, including your age and gender, your diet and where you live. For example, I eat a vegetarian diet, which means I eat a lot of fibre. Humans don’t have all the tools (what scientists call enzymes) necessary for digestion of these carbohydrates. Therefore, you need bacteria in your gut to break down the more complex parts of your food. In my gut lives an abundance of bacteria whose job it is to break down the fibre I eat into smaller molecules that I can absorb and use in my metabolism.


Research has shown that a plant-based diet promotes a more diverse and stable microbial system, with higher amounts of bacteria containing these fibre-crushing enzymes compared to omnivores. In other words, your diet impacts the composition of your microbiota. Just like you might like to be in a nice place where you can eat your favourite meals, these bacteria also have certain food that they prefer or maybe even need to be able to live in your gut. If you eat less fibre, you are essentially starving the fibre-eating bacteria: they will become unhappy and eventually, they will die, leaving you with a smaller population of fibre-eating bacteria in your gut. At the same time, increasing your fibre intake makes your gut more favourable for these bacteria to live in, and they might move back in. The same is true for other food components – if you eat more (or less) sugar, fats, proteins, or even dirt, that will probably affect your microbiota too.


Furthermore, the bacteria living in your gut are guests, so your body sets rules for their stay to keep your gut healthy. Your brain plays a crucial role in enforcing part of these rules as the landlord of your body. Via nerve signals traveling from your brain to your gut, your brain can influence the “police unit” in your intestine: the immune system. This police force plays an important role in regulating which bacteria can and cannot stay in your intestine. In this way, you can keep the bad guys – the ones that can make you sick – out of the city and prevent them from disturbing the community and taking over your gut.


To make it more complicated, this also goes the other way around: your microbiota influences your body too. As tenants, the bacteria also like to let the landlord know what happens in their community. These bacteria can influence all kinds of processes in your body, like your metabolism, brain function and immune reactions.


For example, your microbiota are essential in educating the police officers of your gut – the immune cells. When you’re just a baby, bacteria already move into your gut, and your immune system uses these bacteria to learn which bacteria are the bad guys and which ones you can be friends with. These lessons boost the development of your immune system into a more complex system that is way better at protecting you. How do the bacteria do this? One of their strategies is to produce certain signals that can influence which type of immune cells are made, and therefore turn up or down inflammation.


The police unit is not the only part of your body that the bacterial tenants can affect. Your gut has the important role of absorbing the nutrients you need and, at the same time, keeping the bacteria outside of your body and out of your bloodstream. In other words, it functions as a selective barrier between your body and your environment. Certain nutrients can pass through the city walls to your blood, but bacteria are not allowed to go through the gateway. The most important part of this barrier are the epithelial cells lining your gut. These cells form the bricks of the city walls. They hold on to each other really tightly so no unwanted molecules and pathogens – the bacteria that can make you sick – can cross. So, where do your microbiota come in? Well, some microbes in your gut have the power to strengthen the connections in your city wall – protecting you against the invasion of pathogens – and others can weaken it.

 

Okay, now we know that the bacteria in your gut can influence both your gut itself and your immune system. However, the influence of your microbiota reaches way further than your gut. Signals from these bacteria can even reach your brain! That’s right, these bacteria can affect your brain and, therefore, also your behaviour, cognition and mood. So, how are these messages sent? Research suggests that it all comes down to… poop and corpses. Yes, the bacteria do this with their poop – the metabolites they make after digesting things like fibre – or parts of their body that they lose.

 

There are three main routes that bacteria living in the city of your gut can use to send messages to the brain: (1) via the blood, (2) via the immune system and (3) via nerves. Let’s look at them one by one.



The first route is via the blood flow. Metabolites made by the microbes in your gut can pass the epithelial barrier, crossing the wall of bricks and getting access to your blood. Your blood flow will spread them to other parts of your body, including your brain – like driftwood in a river. Research shows that some of these metabolites can dramatically change your behaviour. For instance, certain metabolites can serve as building blocks for reactions and communication in the brain.

 

As mentioned earlier, metabolites are not the only things reaching the brain via the blood – you might find a limb or two in there as well. In other words, certain parts of the bacteria also use the blood flow to float through your body. In the worst case scenario, if these components get to the brain, they can activate neuroinflammation - inflammation of the brain - because the immune cells in your brain sense the bits of bacteria and think there is an infection. This triggers an immune reaction that can lead to unwanted effects in all kinds of ways – something I’ll get back to in the next post of this series!

 

Alongside the bacterial poop and corpses, there’s actually another type of message that the microbes can send from the gut to the brain – but for this type, they make the gut do the work. Some bacteria can increase or decrease the production of hormones by your gut. These hormones can also enter the bloodstream, and eventually enter the brain. There, they have the power to affect your mood, your memory and even your learning abilities.

 

The second way for bacteria to communicate to the brain is via the immune system. As I explained earlier, your microbiota are important in the development of your immune system. This also applies to the immune cells in your brain. The microbiota are necessary for the training of the police unit in your brain, the microglia, just as they help train the police unit in your gut. On the other hand, certain metabolites produced by your microbiota can activate the immune cells and send more of them to your brain, giving them VIP access to the party in the house of the landlord. When this party gets too big it gets out of hand - causing inflammation in your brain, or neuroinflammation, and changes in your brain function. Keep in mind that this is not the whole story; there are many other ways the bacterial tenants can affect your immune system. For example, they influence the chemical messages the immune cells send to the brain – the mail they send to the house of the landlord.  


And last, we come to the third way of information transport from the gut to the brain: by nerves connecting your gut with your brain. Your gut contains a whole nervous system, that is so complex it is often referred to as your second brain. It comprises around 500 million neurons – the building blocks of this nervous system. To give you a sense of scale, that’s even more than the 448 million people living in the European Union.


How do messages travel across neurons? It starts when metabolites from the bacteria in your gut are recognized by the cells of your gut by sensors we call receptors. Depending on what the gut cells sense through their receptors, these gut cells can send out corresponding signals to neurons, including neurons in one particular, super important nerve: the vagus nerve. The neurons in the vagus nerve form a highway between the gut and the brain. Along this highway, truckloads of information are transported at top speed from the gut to the brain in the form of nerve signals. Thanks to this constant communication, the brain knows what’s going on in the gut. The brain can then react to changes in the gut, for example by modulating digestion and the immune response.


So, as your diet influences your microbiota, and your microbiota control your behaviour, there is a certain truth in “we are what we eat”. I hope this post convinced you of the wonders of the gastrointestinal tract, and that next time you have dinner, you think about the millions of microbial tenants helping you every day! 


Knowing these microbes can influence your brain, you might think “What about when the tenants are acting up?” Indeed, more and more evidence suggests that dysbiosis – a disruption of the microbial community in your gut – leads to imbalances in, for example, neurotransmitter systems and your immune system. This can have huge effects on your brain and, therefore, plays an important role in several brain disorders, including depression, neurodegenerative diseases and autism spectrum disorder. In the next blog post of this series, I will go into the effects of dysbiosis (imbalances in the microbiota) on the integrity of the city (the gut) and the landlord (the brain) in people with autism spectrum disorder.


 

Here is some recommended reading – articles that inspired me while writing this blog post:


  1. The gut microbiota-brain axis in behaviour and brain disorders. Nat Rev Microbiol. 2021. https://www.nature.com/articles/s41579-020-00460-0#Sec8

  2. The role of short-chain fatty acids in microbiota–gut–brain communication. Nat Rev Gastroenterol Hepatol. 2019. https://www.nature.com/articles/s41575-019-0157-3#Sec3 


As I'm not a native English speaker, I used Chat GPT for checking grammar and asking for synonyms. This helped me improve my language and find the right words in English to convey what I wanted to explain to you.   Acknowledgements 

I’m extremely grateful to Alex for all her help throughout my project. I could not have embarked on this blog writing journey without her feedback, enthusiasm and guidance. I am also thankful to Kristin Denzer for her mentorship as my Honours coordinator and for her feedback on my writing. Lastly, I would like to extend my sincere thanks to Lucía Peralta Marzal, my lab supervisor, for the amazing internship experience that laid the foundation for this project and for her insightful feedback on my writing.


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