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The brain–gut axis is a two‑way communication line. The brain can influence digestion, and the gut, in turn, sends signals to the brain via nerves, hormones, immunity and substances produced by microbes, which is why in this article we're talking about the microbiota–gut–brain axis rather than just the “gut–brain” axis.
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When this axis is in balance, it supports the body's “inner calm” (digestion, stress, sleep, appetite and mood); when it is disrupted, problems can manifest not only in the abdomen (e.g., functional issues/IBS) but also in mental health, sleep and weight regulation.
You might know the feeling, too. Under stress, your digestion rumbles, before an important event, you feel “butterflies in your stomach,” and sometimes it seems that when your “stomach is off,” your mind is too. This isn’t just a figure of speech. There really is a two‑way connection between the brain and the gut, in which gut microorganisms play a significant role — the gut microbiome. This network is called the microbiota–gut–brain axis.
What is the brain–gut axis, and where does the microbiome fit in?
You can think of the brain–gut axis as a communication line.
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The brain can influence the gut (for example, through stress responses, changes in the autonomic nervous system and changes in gut motility).
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The gut can influence the brain (via nerve signals, hormones, immune mediators and substances produced by microbes).
The microbiome also comes into play because bacteria in the gut produce substances and signals that can influence the gut environment, immunity and messages sent to nerves and hormones. That’s why this article discusses the “microbiota–gut–brain” axis, not just the “gut–brain” axis.
How do the gut and brain communicate?
The body has several ways to transmit information:
Nerve pathway: The most well‑known is the vagus nerve. It’s like a cable that collects information from the gut and sends it to the brain, and vice versa.
Hormonal and stress pathway: When you’re stressed, the stress system (HPA axis) is activated, changing digestion, gut sensitivity and perception of discomfort.
Immune pathway: The gut is a huge immune crossroads. When in balance, immune signals are calm. When disrupted (e.g., by long‑term poor diet or inflammation), signals can shift toward irritation and inflammatory activity.
Metabolites from the microbiome: Bacteria produce substances like SCFA (short‑chain fatty acids), which can act on the gut wall, nerves and hormones.
Why is the gut sometimes called the second brain?
Within the wall of the digestive tract is a dense network of nerves called the enteric nervous system (ENS). It’s so extensive and independent that it can locally control many functions (e.g., gut motility), yet it’s still connected to the brain. Reviews describe the enteric nervous system as an important hub that collects signals from the gut and communicates with the brain, among other ways, via the vagus nerve and other neural pathways.
The reason ENS is compared to the brain is also that it shares similarities with the central nervous system in structure and the chemistry of communication — they use similar signal transmitters (neurotransmitters).
One of the most well‑known examples is serotonin. Serotonin works both in the brain and in the gut, and can influence many types of processes (not just mood in the usual sense).
Serotonin from the gut does not reach the brain
You may have heard that most serotonin (the happiness hormone) is produced in the gut. That’s true — the body makes a lot of serotonin there.
The important catch is that serotonin made in the gut is not the same as serotonin in the brain. Serotonin from the gut acts mainly locally (e.g., on digestion) and cannot freely enter the brain, because the blood–brain barrier blocks it.
But that doesn’t mean the gut isn’t connected to mental health. It just works indirectly: the gut and microbiome can influence signals to the brain (via nerves, hormones and immunity) and also how much "building material” (tryptophan) the brain has available to make its own serotonin.
What can the brain–gut axis influence?
The brain–gut axis (and microbiome) is mainly a coordination system that helps the body maintain internal balance. When it works well, digestion runs smoothly, immunity responds appropriately and the brain receives reliable signals about what’s happening inside. When communication is disrupted, symptoms often appear not only in the abdomen but also in mood, stress, sleep and appetite. Reviews describe that two‑way interactions between the brain and gut regulate key functions such as food intake, immune regulation and sleep.
1) Digestion and abdominal comfort
Probably the most noticeable part. The brain and nervous system can adjust, depending on the situation:
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The speed of food movement through the gut (some people run to the toilet under stress, whereas others get constipated)
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Gut sensitivity (cramps, tension, bloating)
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Secretion (how actively the gut works)
If the axis is disrupted long‑term, a combination of problems typically appears: irregular stools, sensitivity to certain foods and feelings of discomfort without a clear cause. In disorders like IBS (irritable bowel syndrome), it’s described that dysregulation of these interactions is linked to changes in motility, sensitivity, immunity and mood.
2) Stress response
Under stress, the body switches to alert mode. This happens automatically via the autonomic nervous system (sympathetic/parasympathetic) and hormonal stress pathways. These systems can change gut activity (motility, blood flow, sensitivity) — and the gut, in turn, sends signals back.
A very important player here is the vagus nerve, which collects information from organs and sends it to brain centres. The vagus is largely an incoming line (about 80% of fibres carry information to the brain), so the brain receives lots of messages about the state of the internal environment.
3) Mood, emotional tuning and internal feelings
The brain doesn’t just process what you see and hear. It constantly processes signals from inside the body (gut tension, hunger, nausea, pressure). This is called interoception — internal perception of the body’s state — and the gut is one of the main sources of these signals. These reflex loops aim to maintain balance in the body during changes.
This can have a fairly direct impact on mental health. When your body feels good, it’s easier to stay calm. When the body repeatedly sends signals of discomfort, the brain can become more irritable, tired and sensitive to stress. When the axis is dysregulated, in addition to gut changes, mood changes also appear.
Digestive issues are often linked to anxiety or depression
In population‑based and prospective studies, it is repeatedly shown that people with functional gut disorders (typically IBS) more often report anxiety and depressive symptoms than those without these issues — and the more pronounced the gut symptoms, the higher the mental burden. Some longitudinal studies also suggest bidirectionality. Long‑term stress and anxiety increase the risk of developing or worsening gut problems, and persistent gut discomfort increases the likelihood of worsening mood.
4) Sleep and daily rhythm
Sleep isn’t just the “turning off of the brain.” It’s a state in which the body regenerates, repairs, tunes immunity and regulates hormones. So it makes sense that the brain–gut axis is related to sleep.
In practice, it often looks like this: when digestion is upset (bloating, pain, reflux), sleep is worse. And when sleep is worse, stress tolerance, cravings and resilience to abdominal discomfort are also worse. A vicious cycle develops.
Short sleep negatively affects the gut microbiome
Studies show that after several nights of little sleep, the composition of these bacteria can change, and the body may function worse even outside the gut. After just two nights of shortened sleep, scientists observed a shift in the composition of gut bacteria and, at the same time, worsened insulin sensitivity.
In another study, just three nights of extremely short sleep (about 2 hours/night) led to a decrease in microbiome diversity by about a fifth. This is important because diversity is often considered a sign of a more resilient gut ecosystem.
5) Appetite, satiety and weight regulation
The gut sends signals to the brain that influence:
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How quickly satiety occurs
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How intense the hunger is
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How the body responds to certain types of food (sweet, fatty)
The microbiome also plays a role by influencing some signalling substances produced in the gut. For example, some substances are produced thanks to bacteria (such as secondary bile acids), which can trigger the release of GLP‑1 hormone in the gut, thus contributing to food intake regulation and metabolic balance.
Older human studies have shown that the microbiome of people with obesity differs on average from that of lean individuals. For example, Ley et al., described a lower relative abundance of Bacteroidetes in obese individuals compared to lean ones, and a shift toward a leaner profile during weight loss.
6) Immunity and the body's inflammatory state
A large part of immunity resides in the gut and communicates with the nervous system. If the immune response in the gut is activated, inflammatory signals (cytokines) are produced, which can affect the brain in two ways: either they enter the circulation and act in the brain, or they activate nerve endings (e.g., the vagus nerve), thus changing gut–brain signalling.
Disruption of the gut–brain axis (or even the “gut–brain–microbiome” axis) is most often associated with diseases where digestion, pain perception, stress and mood intersect. However, the evidence is not equally strong for all diagnoses — some are well described, others are still being studied.
Disruption of the brain–gut axis: what can it cause?
1) Irritable bowel syndrome (IBS) and other functional digestive issues
Functional digestive issues are long‑term problems such as abdominal pain, bloating, diarrhoea or constipation, where no clear cause is found during examinations (e.g., inflammation, tumour).
IBS is cited in review papers as the most common disorder of brain–gut interactions. Simply put, it’s a dysregulation of communication between the gut, nerves, immunity and brain, which can manifest as changes in motility, sensitivity (pain) and mood.
IBS is also typically associated with high comorbidity with anxiety and depression, with up to ~50% of people meeting criteria for an anxiety disorder also having IBS. What's more, people with IBS are more than three times as likely to meet criteria for an anxiety disorder.
Prospective data suggest bidirectionality, where higher anxiety/depression increases the risk of developing IBS, and conversely, IBS increases the risk of later anxiety/depression.
The same circle includes functional dyspepsia (long‑term symptoms like fullness, pressure and nausea without a clear cause) and other functional abdominal pain syndromes.
2) Mood disorders (mainly depression)
In major depressive disorder (MDD), differences in microbiome composition are repeatedly described in relation to healthy controls (although studies differ in the specifics).
A review even mentions preclinical data where transferring the microbiome from a depressed person to an animal model can induce depressive behaviour, supporting the hypothesis that the microbiome may be one factor in the chain of mechanisms.
3) Anxiety disorders (often together with IBS)
With anxiety, the “gut ↔ anxiety” scenario is common in practice, especially with IBS, where these issues often reinforce each other (see above).
There are also clinical data showing that interventions in the microbiome (probiotics/prebiotics/synbiotics) can reduce anxiety and depressive symptoms in some people, though results are mixed.
Connections under investigation
Preclinical and clinical findings link the gut–brain–microbiome system with possible mechanisms in some neurological and neurodevelopmental diagnoses, for example:
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Autism spectrum disorder (ASD)
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ADHD
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Parkinson’s disease
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Alzheimer’s disease
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Multiple sclerosis
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Epilepsy
For these diseases, it often means there are signals and hypotheses, not that they can be simply treated this way.
What usually benefits the microbiome–brain–gut axis
The microbiome is a very rich ecosystem. The goal is to create an environment where a more diverse and stable composition thrives long‑term. The good news is that the things that usually benefit it are mostly the same things that benefit the body as a whole.
1) A diet rich in prebiotics and polyphenols
You can think of prebiotics and polyphenols as fuel for the gut microbiome. These are substances that are often not fully digested in the small intestine, so they reach the large intestine, where they are used by "good" bacteria. That’s why they are considered one of the simplest ways to support the microbiome through regular food. You’ll find the most in plant foods, especially when your diet is varied.
For example, in a study with healthy volunteers, 3 weeks of prebiotic B‑GOS (Bimuno galactooligosaccharides) led to a lower morning cortisol response after waking (a marker of the stress axis) and a shift in emotional processing — after B‑GOS, people paid less attention to negative stimuli and relatively more to positive ones.
Rich sources of prebiotics and polyphenols
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Legumes: lentils, chickpeas, beans, peas (including hummus, soups and spreads)
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Whole grains: oat flakes, rye, barley, whole grain and rye bread
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Root and “onion” vegetables: onion, garlic, leek, spring onion
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Berries: blueberries, raspberries, strawberries, blackberries, currants
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Cocoa and dark chocolate (higher cocoa content)
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Coffee and tea (green and black)
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Olive oil (extra virgin) and olives
Image by freepik.com
2) Mediterranean style of eating
The microbiome usually benefits from variety in plant foods, quality fats and fewer ultra‑processed foods. This fits perfectly with the Mediterranean diet (vegetables, fruit, legumes, whole grains, nuts, fish, olive oil).
In the SMILES study, the group with dietary support (Mediterranean diet) had significantly greater improvement in depressive symptoms than the control group and more often achieved remission (about 32% vs. 8%). The authors state that the differences were not explained by changes in BMI or physical activity, so it wasn’t just about weight loss.
In another PREDIDEP study (Mediterranean diet + extra virgin olive oil), the main goal (relapse prevention) did not differ, but as a secondary outcome, there was improvement in depressive symptoms at months 4 and 8 (and also a difference at month 20).
3) Fermented foods
Fermented foods (yoghurt, kefir, sauerkraut, etc.) can be a great addition to the diet.
One study focused on a diet rich in fermented foods showed that this style of eating can increase microbiome diversity and, at the same time, reduce some inflammatory proteins in the blood.
In another study involving healthy women, 4 weeks of consuming a fermented dairy product with probiotics led to changes in the activity of brain areas related to processing emotions and bodily sensations, and also changed some indicators of resting brain connectivity.
4) Sleep and stress management
The microbiome is influenced not only by what you eat. Stress and sleep also affect the gut. Reviews directly state that the microbiome regulates the stress axis (HPA), but the reverse is also true: when the stress axis changes, so does the microbiome. For example, in “germ‑free” mice (mice without a microbiome), the HPA axis stress response is exaggerated, and after colonisation with microbiota, it can normalise, especially if colonisation occurs early after birth.
In humans, it is shown that long‑term psychological stress is associated with shifts in the microbiome over time. Among healthcare workers exposed to strong stressors during COVID‑19, dysbiosis and microbiome changes were described, persisting for at least half a year and related to the degree of post‑traumatic/stress symptoms.
Omega‑3 fatty acids can also help
Omega‑3 fatty acids can gently influence the gut–brain axis through the microbiome, gut barrier and signals that travel from the gut (hormones, metabolites, immunity). In observational data, it appears that people with higher omega‑3 status (especially DHA in the blood) tend to have higher microbiome diversity and different representation of some bacterial groups.
Intervention studies in humans show a slight shift in the microbiome. After omega‑3 supplementation, there is a repeated increase in some groups associated with SCFA production (e.g., Bifidobacterium, Roseburia), or a decrease in genera more common in pro‑inflammatory/metabolically unfavourable contexts.
What effect can probiotics have?
Probiotics are live microorganisms that, when administered in adequate amounts, contribute to the health of the host.
A meta‑analysis of 72 studies found that probiotics (and related interventions) on average led to fewer depressive symptoms, less anxiety and, with probiotics, also to slightly better sleep compared to controls.
However, results vary greatly between studies (different strains, doses, people), so it doesn’t work the same for everyone, and study quality isn’t always ideal (only a minority of studies had a low risk of bias).
Bottom line
The brain–gut–microbiome axis is a real connection. Stress can disrupt digestion and gut health can, in turn, affect mood, sleep and appetite. The biggest difference usually doesn’t come from a single supplement, but from a long‑term foundation like a varied plant‑based diet (filled with fibre, prebiotics, polyphenols), enough sleep and stress management. If you want something extra, you can try fermented foods or probiotics, but treat them as a bonus with individual effects, not as the main solution.
