This is one of the most repeated and most distorted slogans of recent years. The term “second brain” started as a short way to describe the anatomy of the digestive tract. The media turned it into an explanation for almost everything. Below, we separate anatomical facts from the results of animal studies and from what is simply not known.
The enteric nervous system – anatomical facts
The wall of the digestive tract contains a large network of nerve cells (neurons), called the enteric nervous system. It has two main parts, called plexuses: the myenteric plexus, between the muscle layers, and the submucosal plexus, closer to the mucous membrane.
Estimates of the number of neurons in this network are in the hundreds of millions, and they differ depending on the counting method. This is much less than in the brain, where the number is in the tens of billions.
What makes this network special is that it can control the work of the gut locally. The reflexes that move food along and control secretion can happen in the gut wall itself, without the brain or the spinal cord.
This independence is the source of all the confusion about the term. The enteric nervous system works on its own when it controls movement and secretion, not thinking or feeling emotions.
Where the second brain metaphor came from and why it is misleading
The term became popular through a popular science book published in 1998 by the neurogastroenterologist Michael Gershon. It was meant to describe the independence of the enteric nervous system, not to suggest that the gut thinks.
In public, the metaphor started to live its own life. The short description turned into the claim that the gut “decides” your mood. This is a completely different idea from the one that anatomy describes.
So it is worth saying clearly what the enteric nervous system does not do. It does not process information in a way that is similar to the cerebral cortex. It does not create emotions or thoughts, and it has no structures for conscious processing of stimuli.
The metaphor is useful as a picture of how independent this network is. If you take it literally, it leads to conclusions that you cannot defend.
How the gut and the brain communicate
The digestive tract and the central nervous system communicate in both directions and in several ways. Below are the three best described ways.
The vagus nerve
The vagus nerve connects the internal organs with the brainstem, and it is the main nerve pathway in this communication. Most of its fibres are sensory fibres, which carry signals from the organs to the brain.
These signals are about the state of the digestive tract: how much the wall stretches, whether food is present and the chemical conditions. The body uses them to control digestion and the feeling of fullness.
Receiving these signals is not the same as feeling them consciously. Most of this communication happens without our awareness.
Chemical signals
The second pathway is compounds in the blood: hormones of the digestive tract, bacterial metabolites and substances made during digestion. Some of them act on receptors outside the gut.
The key limit is the blood-brain barrier, a structure that controls which substances can pass from the blood into brain tissue. Not every compound in the blood can reach the brain. This is very important when you assess reports about the effect of the gut on the brain.
The immune system
A large part of the cells of the immune system are in the digestive tract, and substances involved in inflammation can act on the nervous system. This is the third described pathway of communication.
Read more: Microbiota and the immune system – what research says about this link
Most detailed observations in this area come from animal models and in vitro studies, that is studies on cell cultures outside the body. Separate clinical studies are needed to show whether they apply to humans (Belkaid and Hand, 2014).
Serotonin in the gut – the most common misunderstanding
This is the most repeated argument in texts about the gut-brain axis, and also the most distorted one. It is a fact that most of the serotonin in the human body is in the digestive tract. There, it is made mainly by enterochromaffin cells in the mucous membrane.
But people draw a conclusion from this fact that does not follow from it. Serotonin made in the gut does not cross the blood-brain barrier, so it does not add to the serotonin in the brain. Brain serotonin is made locally in the nerve cells of the central nervous system, from tryptophan that comes from food.
Serotonin outside the brain has its own functions in the digestive tract, for example in controlling movement and secretion. These are local tasks, with no direct link to its role as a neurotransmitter in the brain.
The sentence “most serotonin is made in the gut, so the gut controls mood” connects two true facts with a false conclusion. This is the most common logical error in popular texts on this topic.
What animal studies show and what has not been confirmed in humans
Most of the impressive results in this area come from studies on mice, and we need to say this clearly. Animal models allow experiments that are not possible in humans: raising animals without a microbiota or moving the microbiota from one animal to another.
| Observation in an animal model | Status of data in humans |
|---|---|
| Changes in behaviour in mice without a microbiota | No equivalent, this model cannot be repeated in humans |
| Changes in behaviour after moving the microbiota between mice | Not confirmed in clinical studies |
| Effect of cutting the vagus nerve on the observed effects | Limited data in humans, from other clinical contexts |
| Changes in stress measures after giving selected bacterial strains | Few studies with people, in small groups, with different methods |
For more than ten years, researchers have tried to apply these observations to humans, for example under the name psychobiotics. These are early studies in small groups and with different study designs, so they do not allow practical conclusions (Dinan et al., 2013).
We need to say this clearly: current knowledge does not support the claim that a diet or any product can affect mental disorders. For questions about your mental well-being, the right person to talk to is a doctor or a psychologist. A change in diet is not the answer.
Where over-interpretation starts
Over-interpretation usually starts in one of three places. The first is when a result from mice is applied to humans without saying that it is a different organism and different conditions.
The second is when a correlation is presented as a cause. Observational studies in humans describe things that happen together. But they do not show the direction of the link, and they do not rule out a third factor, for example diet.
Read more: Gut microbiota – how it develops and what shapes it throughout life
The third is when a conclusion about a specific strain is applied to a whole category of products. The properties described in studies refer to a named strain and do not automatically apply to others.
How to read headlines on this topic
A few questions help you quickly judge the value of a report:
- Who was studied? Mice, a cell culture or people. This difference changes the meaning of the result the most.
- How many people took part? Studies in this area often include between ten and a few dozen people.
- Was it controlled? Without a comparison group, we do not know what would have happened without the intervention.
- What exactly was measured? A change in a questionnaire score is not the same as a change in a clinical condition.
- Does the conclusion refer to the same material? A specific strain and “gut bacteria” are two different levels of detail.
- What does the original publication say? The media sometimes change “may be linked to” into “causes”. Read more: What has a negative effect on the gut microbiota – diet, stress, medicines, sleep
Summary
The enteric nervous system exists and is large, and its independence in controlling movement and secretion is an anatomical fact. The term “second brain” describes exactly this independence. If you take it literally, it is misleading.
The gut and the brain communicate in both directions, through nerves, chemical signals and the immune system. But this does not mean that the state of the gut controls mood. The serotonin argument is based on a false conclusion, because gut serotonin does not cross the blood-brain barrier.
Most of the impressive observations come from studies on mice, and studies with people are few, early and in small groups. They do not support practical conclusions. For questions about your mental well-being, talk to a doctor or a psychologist.
FAQ
Does the gut affect mood?
The careful answer is this: there are pathways of communication between the digestive tract and the brain, but the claim that the state of the gut determines mood goes beyond what studies have shown. Digestive problems that do not go away can affect how you feel, like any other long-lasting health problem. This is different from the idea that the microbiota controls emotions. If you have problems with your mental well-being, contact a doctor or a psychologist.
Is the gut really a second brain?
Not literally. The enteric nervous system can control the work of the gut on its own, but it does not process information in a way that is similar to the brain, and it does not create emotions or thoughts.
If serotonin is made in the gut, does diet change its level in the brain?
This does not follow from the fact that most serotonin is in the digestive tract. Serotonin outside the brain does not cross the blood-brain barrier, and brain serotonin is made locally from tryptophan. These are two separate pools with different functions.
Is research in this area worthless?
No. It is an active and justified area of research, but it is at an early stage. The difference is that a result from an animal model is a reason for further research, not a basis for practical advice.
Sources
- Furness J.B., The enteric nervous system and neurogastroenterology, Nature Reviews Gastroenterology & Hepatology, 2012, vol. 9, no. 5, pp. 286-294.
- Gershon M.D., The Second Brain, HarperCollins, New York 1998.
- Berg G., Rybakova D., Fischer D. et al., Microbiome definition re-visited: old concepts and new challenges, Microbiome, 2020, vol. 8, no. 103.
- Commission Regulation (EU) No 432/2012 of 16 May 2012 establishing a list of permitted health claims made on foods, other than those referring to the reduction of disease risk and to children’s development and health.
- Dinan T.G., Stanton C., Cryan J.F., Psychobiotics: a novel class of psychotropic, Biological Psychiatry, 2013, vol. 74, no. 10, pp. 720-726.
- Belkaid Y., Hand T.W., Role of the microbiota in immunity and inflammation, Cell, 2014, vol. 157, no. 1, pp. 121-141.
- Yano J.M., Yu K., Donaldson G.P. et al., Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis, Cell, 2015, vol. 161, no. 2, pp. 264-276.
- Braniste V., Al-Asmakh M., Kowal C. et al., The gut microbiota influences blood-brain barrier permeability in mice, Science Translational Medicine, 2014, vol. 6, no. 263, 263ra158.