The interactions between the gut and the brain, also referred to as the gut-brain axis, represent a very interesting area of research in modern medicine. It connects the central nervous system (CNS) with the enteric nervous system (ENS). The gut-brain axis plays an important role in the regulation of metabolic processes, the immune response, and even mental health.
Hard to believe, but while the brain has about 86 billion neurons, the gut with its enteric nervous system (ENS) – consisting of around 100 million nerve cells – is similarly complex. This nervous system operates largely autonomously, controlling digestion, processing signals, and mediating reflexes. However, it also continuously interacts with the central nervous system (CNS), highlighting the importance of the gut as a "second brain" .
In addition to the neuronal density, the ENS is closely linked to the CNS through chemical messengers, electrical impulses, and immune cells. These networks influence not only physiological processes but also emotional states and cognitive functions. It is indeed a very exciting field of research, which is already much better understood than it was ten years ago. However, it is still largely considered a "black box," and we can expect many more exciting insights from the research of this connection, which have the potential to change both basic medicine and therapeutic approaches.
What components play a role in the gut-brain axis?
At the beginning, this overview is meant to give you an idea of which components in our body are interconnected in the gut-brain axis and thus also influence each other. A whole orchestra of processes is formed here, and if one does not play in time, it can affect the entire piece. In the following text, we will go into more detail about the respective players.
Neural communication
- The vagus nerve is the most important direct connection between the gut and the brain. It transmits signals in both directions and influences, among other things, digestion, emotions, and stress levels.
- The enteric nervous system, also known as the "gut brain," independently regulates many functions of the gastrointestinal tract.
Microbiome and Metabolites
- The trillions of microorganisms in the gut (microbiome) produce neurotransmitters such as serotonin, dopamine, and GABA, which can directly influence the brain.
- Short-chain fatty acids such as butyrate, propionate, and acetate have immunomodulatory and neuroprotective effects.
Endocrine (hormonal) Communication
- The gut produces hormones such as ghrelin, leptin, and peptide YY, which influence appetite, mood, and metabolism.
- The hypothalamic-pituitary-adrenal axis (HPA axis) responds to stress and can be influenced by inflammation or gut dysbiosis.
Immunological Interaction
- The gut is equipped with about 70% of the immune system.
- A disturbed gut barrier (Leaky Gut) can trigger inflammatory processes that are associated with neurological and psychological disorders.
The vagus nerve as the main connection
The vagus nerve is the longest and perhaps the most important nerve of our autonomic nervous system. It connects the brain with almost all vital organs – from the heart to the lungs to the gut.Previously, the vagus nerve was primarily researched in neurology and cardiology, but today it is becoming increasingly clear that it is not only responsible for the control of organs but also influences our mood, our immune system, and even chronic inflammation. It is no wonder that the vagus nerve is currently gaining enormous attention – both in science and in the media.
How does the vagus nerve affect the gut?
The vagus nerve is the direct communication pathway between the gut and the brain. Its fibers transport 80% of the signals from the gut to the brain – and only 20% in the other direction. This shows how strongly the brain is influenced by information from the digestive tract.These signals regulate numerous processes:
Digestion and intestinal movement
The vagus nerve controls the motility of the intestine by regulating the peristalsis (the rhythmic contractions of the intestine). If it is weakened, this can lead to digestive problems such as constipation, bloating, or even irritable bowel syndrome (IBS, Inflammatory Bowel Disease).
Anti-inflammatory and immune system
It activates the cholinergic anti-inflammatory reflex, a body’s own protective system against inflammation. If this mechanism is disturbed, chronic inflammation can occur, which plays a role in Crohn's disease, ulcerative colitis, or autoimmune diseases.
Influence on mood and the nervous system
The vagus nerve influences the production of neurotransmitters such as serotonin, dopamine, and GABA, which are important for our mood and mental performance. Disturbed vagus activity is associated with depression, anxiety disorders, and even neurodegenerative diseases such as Parkinson's.
Communication with the microbiome
Gut bacteria produce substances that are transmitted to the brain via the vagus nerve. A dysbiosis (imbalance in the microbiota) can lead to cognitive and emotional disorders through this mechanism. Dysbiosis is also one of the 12 characteristics of aging.
TENS training is also a variant of neuromodulation that works similarly to vagus nerve stimulation. However, in vagus nerve stimulation, the electrodes are placed more on the ear, neck, or wrist.
How can the vagus nerve be stimulated?
Since the vagus nerve is deeply involved in many bodily processes, research has intensively explored possible forms of therapy. Some of these are already officially approved or are being clinically tested. This field is also summarized as neuromodulation, about which we have already written a separate article.
Vagus nerve stimulation (VNS) – Electrical activation of the nerve
Vagus nerve stimulation (VNS) is a medically approved therapy.This involves stimulating the nerve through electrical impulses – either via an implanted device or through a non-invasive method (e.g., through the ear region). This therapy is used for:
- Epilepsy
- Therapy-resistant depression
- Cluster headaches
- (Researching for) Irritable bowel syndrome &and chronic inflammation
Polyvagal therapy (Stephen Porges’ Polyvagal Theory)
Focused on activating the “ventral vagus” to reduce anxiety, trauma, and digestive disorders.Applied techniques include breathing exercises, meditation, body exercises, and pressure points.
Natural methods for vagus nerve stimulation
- Deep breathing: Longer exhalation activates the parasympathetic nerve.
- Cold exposure: Alternating showers or ice baths increase vagus activity. Especially the extreme athlete Wim Hof has made this practice very well known and has written several books about it.
- Singing, humming, gargling: Activates the vagus nerve through the larynx.
Why is the vagus nerve so present in the media right now?
The vagus nerve is currently on everyone's lips – both in scientific research and in the press. The reasons for this are diverse:
- Increase in stress-related illnesses: Chronic stress and burnout are increasing worldwide, and the vagus nerve offers a natural way to calm the nervous system.
- New insights into the treatment of chronic inflammation: Studies show that low vagus activity is associated with silent inflammation (low-grade inflammation, or Inflammaging), which plays a role in autoimmune diseases, diabetes, and cardiovascular diseases.
- Trend in self-optimization &and biohacking scene: The vagus nerve is celebrated as the "super nerve" – and methods such as breathing techniques, cold baths, and vagus-activating nutrition and exercises have become popular trends.
The role of the gut microbiome
The gut microbiome as a key player in the gut-brain axis
The gut microbiome - the trillions of bacteria, viruses, and fungi that live in our gut, have a direct influence on the communication between gut and brain.These microorganisms produce a variety of neurotransmitters, hormones, and metabolites that communicate with the brain via the vagus nerve, the immune system, and the endocrine system.
Healthy microbiota promote mental well-being, while dysbiosis is associated with mental and neurological disorders – thus affecting mood, stress levels, and even concentration. Overgrowths of pathogenic microorganisms such as Candida or SIBO (Small Intestinal Bacterial Overgrowth) often lead to symptoms such as bloating, diarrhea, and nutrient deficiencies. What substances are produced in the gut, what influence do they have, and which bacteria play a special role in this? We will take a closer look at these questions now.
What substances are produced by the microbiome that are involved in gut-brain communication?
The communication between the gut and the brain occurs via three main mechanisms:
1) Production of neurotransmitters and neuromodulators
Certain gut bacteria directly produce neurotransmitters that play a central role in our mood, cognition, and gut motility. These include:
Serotonin (5-HT) – "happiness hormone"
- 90% of the serotonin in the body is produced by enterochromaffin cells in the gut, which are regulated by gut bacteria.
- Producing bacteria: Escherichia coli, Enterococcus, Streptococcus, Lactobacillus and Bifidobacterium.
- Function: Regulates mood, sleep, appetite and bowel movement.
- Dysbiosis effects: A serotonin deficiency can be associated with depression, anxiety disorders, and irritable bowel syndrome (IBS).
Dopamine – "Motivation hormone"
- Produced by Bacillus spp. and Escherichia coli.
- Function: Influences motivation, reward system, and motor control.
- Dysbiosis effects: Dopamine deficiency is associated with Parkinson's, depression, and ADHD.
GABA – "Relaxation hormone"
- Produced by Lactobacillus and Bifidobacterium.
- Function: Inhibits the nervous system, reduces stress and anxiety.
- Dysbiosis effects: A low GABA level is associated with anxiety disorders and depression.
Acetylcholine – "Learning and memory hormone"
- Produced by Lactobacillus spp.
- Function: Promotes memory processes and regulates the autonomic nervous system.
2) Production of short-chain fatty acids
Short-chain fatty acids are important metabolic products of the microbiome that have a direct impact on the brain.
Butyrate (produced by Faecalibacterium prausnitzii, Roseburia and Eubacterium rectale). Has anti-inflammatory effects, protects the gut barrier, and promotes the production of the brain-derived neurotrophic factor BDNF (important for learning &and memory).
Propionate &and Acetate binfluence energy metabolism in the brain.
3) Modulation of the immune system and inflammatory responses
The microbiome regulates the immune system through certain substances and influences the blood-brain barrier as well as inflammatory processes:
Lipopolysaccharides (LPS) (from gram-negative bacteria such as Enterobacter and Escherichia coli)
- Can damage the intestinal barrier ("Leaky Gut") and trigger inflammation throughout the body.
- Dysbiosis effects: Chronic inflammation caused by LPS is associated with depression, anxiety disorders, Parkinson's, and Alzheimer's.
Tryptophan metabolites (e.g., indole, kynurenine)
- Determine whether tryptophan is metabolized to serotonin (good) or neurotoxic kynurenines (bad).
- An imbalanced tryptophan metabolism is associated with sleep disorders, depression, and cognitive impairments.
Hormones and neurotransmitters: The biochemical language of the gut
The gut is a central endocrine organ and produces a variety of hormones that not only regulate digestion but also influence hunger, satiety, metabolism, and even mood.About the gut-brain axis, these hormones communicate directly with the brain and influence our behavior as well as physiological processes throughout the body.
Hunger and satiety hormones
The gut plays a crucial role in regulating appetite:
Ghrelin – the hunger hormone
- Produced in the stomach and small intestine, ghrelin increases appetite by signaling to the brain that it is time to eat.
- Its level rises before a meal and falls after food intake.
Peptide YY (PYY) – the satiety hormone
- Is released in the lower small intestine and upper large intestine and signals to the brain that enough food has been consumed.
- It inhibits gastric emptying and reduces feelings of hunger.
Glucagon-like Peptide-1 (GLP-1) – the metabolic regulator
- Promotes insulin secretion and inhibits glucagon release, thereby lowering the blood sugar level.
- Slows gastric emptying, resulting in a longer-lasting feeling of satiety.
- Due to its effect, GLP-1 is a key component of modern medications for the treatment of diabetes, obesity, and insulin resistance.
Cholecystokinin (CCK) – the digestive aid
- CCK is produced in the I-cells of the small intestine and plays a dual role: it stimulates the release of digestive enzymes from the pancreas and simultaneously promotes the feeling of satiety.
Digestive-regulating hormones
In addition to regulating appetite, the intestine also regulates numerous digestive processes:
Gastrin sstimulates the production of gastric acid to promote the digestion of proteins.
Secretin is released upon contact with acidic stomach contents in the small intestine and ensures that the pancreas produces bicarbonate to neutralize stomach acid.
Motilin regulates the so-called Migrating Motor Complexes (MMC), rhythmic contractions that occur between meals and cleanse the intestine. This function is currently a major focus of research and plays a special role in dysbiosis and irritable bowel syndrome.
Neuroactive Hormones
The close connection between the gut and the brain is mediated by a number of neuroactive hormones:
Serotonin – the happiness hormone
- About 90 % of the total serotonin is produced not in the brain, but in the gut.
- It regulates gut motility, but also influences the central nervous system and thus mood.
- Disrupted serotonin production is associated with irritable bowel syndrome, depression, and anxiety disorders.
Cortisol (indirectly influenced by gut bacteria)
- Although Cortisol is produced in the adrenal glands, the gut microbiome indirectly regulates the stress response via the HPA axis, neurotransmitters, and the immune system. A healthy gut flora can help cushion cortisol spikes, reduce inflammation, and increase stress resistance – an important key to mental and physical balance.
The immune system and the communication between the gut and the brain
About 70% of all immune cells are located in the gut, where they work in a highly sensitive interplay with the microbiome. If this balance is disturbed, it can have fatal consequences: inflammatory substances from the gut enter the bloodstream and directly affect the brain
But how exactly does the immune system affect the gut-brain axis? And how can one specifically reduce inflammation to protect not only the gut but also the brain?
The gut barrier – your immune defense on the front line
The intestinal mucosa is the first layer of protection against unwanted intruders.She decides which substances are allowed to pass into the blood.
Tight Junctions are tiny proteins that hold the intestinal cells together like a barrier – but during inflammation or dysbiosis, they can become permeable.
“Leaky Gut” (permeable gut) occurs when toxins, undigested food particles, or bacterial components (e.g. lipopolysaccharides, LPS) pass through the intestinal wall into the blood and trigger an immune response.
Inflammation as a silent threat to the brain
If the immune system is out of balance, it releases pro-inflammatory cytokines:
- Interleukin-6
- Tumor necrosis factor-alpha
- Interleukin-1β
These signaling molecules can enter the bloodstream and trigger inflammation in the brain. Chronically elevated cytokine levels are directly linked to depression, anxiety disorders, Alzheimer’s, and Parkinson’s.
The blood-brain barrier – when the immune system attacks the brain
The blood-brain barrier (BBB) protects the brain from toxins – but a disturbed immune response can make it more permeable.Immune cells and inflammatory substances can penetrate the brain and damage nerve cells. This is suspected to be involved in the development of neurodegenerative diseases such as Alzheimer's and multiple sclerosis (MS).
How can you calm your immune system through the gut?
When an overactive immune response attacks the brain, the best strategy is to restore balance to the immune system through a stable gut flora and anti-inflammatory measures.
Strengthen the gut barrier
Fiber (prebiotics) from vegetables, legumes, and whole grains promote healthy gut bacteria and protect the intestinal mucosa. Glutamine &and Zinc repair damaged Tight Junctions and reduce intestinal permeability.
Lower inflammatory responses
Omega-3 fatty acids (fish, flaxseed, algae) have strong anti-inflammatory effects. Polyphenols – a subgroup of secondary plant compounds (berries, green tea, turmeric, dark chocolate) reduce the production of IL-6 and TNF-α.
Probiotics &and fermented foods (sauerkraut, yogurt, kimchi) promote anti-inflammatory gut bacteria.
Immune modulation through the vagus nerve
Breathing exercises, meditation, and cold exposure activate the "cholinergic anti-inflammatory reflex," which systematically reduces inflammation. The vagus nerve regulates the release of anti-inflammatory messengers and acts directly on the immune system.
Conclusion - Gut-Brain Axis
The gut-brain axis is an exciting field of research that goes far beyond digestion – it influences our immune system, our mood, and cognitive performance. New insights into the microbiome and innovative approaches such as personalized nutrition and vagus nerve stimulation could open new avenues for promoting health in the future.
Some things remain unclear, and science is still relatively at the beginning when it comes to fully understanding the complex mechanisms. What is already certain: A healthy gut contributes much more to well-being than was previously assumed – and could be a key to new prevention and therapy options.
