Stress, the brain, and the body’s defence systems
A look at how the issues that we deal with as hypnotherapists are linked to the way the immune system and the digestive system (and its microbiome) work.
Many hypnotherapists are trained to understand that people who are under stress find their phobias getting worse (if they have them) and their OCD (obsessive-compulsive disorder) getting worse (if they suffer with it). There’s no real explanation of what’s going on, just the metaphorical idea of a ‘stress bucket’ filling up. It’s not too much of a problem, because ‘bucket-emptying’ strategies can be used to help those people and make things better.
Wouldn’t it be better to understand exactly what is going on in the body, and have a greater understanding of the defence systems that are used to protect the body, just how closely connected those systems are, and how those systems interact, sometimes resulting in behaviours, emotions, and thinking shown by clients and potential clients. That understanding could lead us to being able to give clients some directly-applicable advice about how to overcome their issues.
The body’s defensive system is illustrated in Figure 1.
Figure 1: The body’s defensive system
The defence systems
The philosopher, René Descartes, in the 17th century came up with the highly-influential idea of Cartesian dualism – the idea that mind and the body are separate entities. This article will look at just how linked the different parts of the body’s defence system really is. In addition to the brain (and the nervous system), we’ll be looking at the immune system and the gut microbiome. The three defence systems that link together to form one holistic system. And we’ll look at how each influences the others.
The immune system
Basically, the immune system can distinguish between cells that are part of the body, ie ‘self’, and cells that aren’t part of the body, pathogens (germs), ie ‘non-self’. As well as receptors that can distinguish self from non-self, there are receptors that can identify threats – pattern recognition receptors (PRRs).
People have an innate immune system and an adaptive immune system. The innate immune system deals with pathogens immediately in a non-specific manner at the site of the infection. The adaptive immune system is slower and more specific using cells that remember specific pathogens.
The main parts of the immune system are:
Lymphatic system – a network of delicate tubes throughout the body. The lymphatic system: manages the fluid levels in the body; reacts to bacteria; deals with cancer cells; deals with cell products that might result in disease or disorders; and absorbs some of the fats in our diet from the intestine. Its main components are: lymph nodes (or lymph glands) that trap microbes; lymph vessels that carry lymph, (a colourless fluid that bathes the body’s tissues and contains infection-fighting white blood cells); and white blood cells (lymphocytes).
Spleen – a blood-filtering organ that removes microbes and destroys old or damaged red blood cells. It also makes disease-fighting components of the immune system (including antibodies and lymphocytes).
Bone marrow – the spongy tissue found inside bones that produces the red blood cells used to carry oxygen, the white blood cells used to fight infection, and the platelets used when blood clots.
Thymus – a primary lymphoid organ in the chest where immature T-cells mature and are selected for appropriate immune recognition and self-tolerance. It’s most active during childhood.
White blood cells – these launch an immune attack on pathogens. Examples include B-cells, T-cells, natural killer (NK) cells, and other types of immune cells.
Antibodies – these immune proteins recognize antigens on the surface of a microbe, or in the chemicals they produce, as being non-self. The antibodies mark the antigens for destruction, which then involves many cells, proteins, and chemicals in the attack.
Complement system – this is made up of proteins whose actions complement the work done by antibodies.
Proteasome – a tiny structure found in every cell of the body. It usually degrades proteins into peptides so they can be recycled to make new ones.
The five signs of inflammation are:
Redness – a sign of inflammation in the skin
Heat – a sign of inflammation in the tissue
Swelling – a sign of inflammation in the tissue
Pain – a sign of inflammation in the tissue
Loss of function – a sign of inflammation in the tissue.
People with inflammation tend to have insulin resistance, leptin resistance, and an imbalance of lipids and cholesterol in the blood.
Let’s suppose that a small cut occurs in the skin. Firstly, macrophages (white cells) use their pattern recognition receptors (PRRs) to lock onto common molecules found on the cell walls of many bacteria. The macrophages secrete cytokines (tiny soluble proteins), which interact with other immune cells. Pro-inflammatory cytokines trigger an inflammatory response. Neutrophils and other cells go to the site of the injury. They can deal with other pathogens entering the cut and start wound healing. Mast cells (a type of granulocyte white blood cells) contain histamine, heparin, cytokines, and growth factors. The histamine causes the red wheals in an allergic reaction. Mast cells dilate blood vessels providing room for more immune cells to get near the site of the injury. Inflammation on the skin is a red, hot, and painful swelling.
Macrophages engulf pathogens and use their enzymes to reduce the pathogen to its proteins. These fragments are called antigens and can be unique to that type of bacterium. The macrophages then travel through the lymphatic system to the lymph nodes. Macrophages present processed antigen fragments on MHC molecules, which are recognized by T-cell receptors; co-stimulatory signals determine activation.
Major histocompatibility complex (MHC) molecules are specialized cell-surface glycoproteins that bind peptide fragments derived from pathogens and display them on the cell surface for recognition by T cells
In fact, lots of T-cells check with the macrophage to see whether they are the right type. The appropriate T-cells then signal to other cells, including B-cells, which produce antibodies against the specific bacteria. The antibodies stick to the bacteria and either block its receptor sites or flag it for destruction by other cells.
In a nutshell, inflammation is the body’s natural immune response to tissue damage, infection, or harmful stimuli,
The brain and the immune system are similar in that they both differentiate between self and non-self, and identify anything threatening in the local environment. The immune system works at the microscopic level, and the brain works at the macroscopic level. Their goals are defence and survival.
Nerves and the immune system
While the peripheral nervous system and the immune system would seem to be quite separate entities, they are, in fact, able to communicate with each other.
T-cells from the immune system help protect crushed neurons in the central nervous system, and mice with impaired immune systems develop neurodegenerative diseases faster than normal mice.
Following a small cut, nerve endings can release inflammatory chemicals, including substance P, which interacts with immune cells, causing (amongst other things) mast cells to burst releasing pro-inflammatory chemicals (including histamine and heparin). Lastly, cytokines produced by immune cells can interact with nerve endings causing an increase in pain sensitivity at the site of the injury.
The immune system and the brain
Sickness behaviour is a coordinated set of adaptive behavioural changes that occur in physically ill people during the course of an infection. These behaviours include lethargy, depressed mood, reduced social exploration, loss of appetite, sleepiness, hyperalgesia (sensitivity to pain), slower movements, reduced ability to experience pleasure, and, at times, confusion. It’s an alteration of the mind in response to a dangerous microorganism being recognized by the immune system.
The outermost layer of the brain is called the dura mater (tough mother). Its job is to drain fluids away from the brain. It does this just below the skull, where the fluid passes into dural sinuses and then into veins in the neck.
Immune cells can enter and leave the meninges of the brain. Interestingly, in 2012, it was discovered that the brain had its own equivalent to the lymphatic system, called the glymphatic system. The name comes from lymphatic (obviously) and glial cells found in the brain. The glymphatic system performs waste clearance through astroglial water channels. In 2015, meningeal lymphatic vessels were discovered.
The fluid compartments in the brain consist of intracellular fluid (ICF) (60-68%), interstitial fluid (ISF) (or extracellular fluid) (12-20%), blood (10%), and the cerebrospinal fluid (CSF) (10%).
The glymphatic system seems to be composed of astrocytes surrounding capillaries that pass through the brain.
Cerebrospinal fluid washes across brain tissue clearing up tiny molecules of waste. This mainly happens during sleep. Dirty CSF then crosses into the dura, which contains immune cells. It was thought that the body’s immune cells couldn’t enter the brain, but they could test the contents of the CSF from the brain to see whether it is infected or inflamed. Many of these immune cells actually come from tiny bone structures connecting the skull to the dura mater. It’s now thought that immune cell can access the brain parenchyma (the functional tissue of the brain), although it’s tightly regulated.
There are many types of glial cells, but microglial cells are different in that they have a mesodermal/yolk-sac origin rather than neuroectodermal origin. They are derived from primitive macrophages in the embryo. Microglia behave like immune cells. They can scavenge and engulf, and they can produce cytokines, and become activated or influenced by immunological molecules. T-cells can pass through the blood-brain barrier and help microglial cells battle infection.
It’s well known that synaptic pruning takes place in the brain. In the immune system, complement proteins attach to microbes or damaged cells and act like an ‘eat me’ signal to macrophages. In the brain, unused synapses are coated with complement proteins, and microglia then engulf and destroy them.
Microglia, the brain’s immune cells, engulf synaptic material in a process named microglial pruning. This suggests that microglia actively sculpt brain circuits by tagging and removing unwanted synapses by phagocytosis.
The blood-brain barrier (BBB) was thought to keep everything in the blood out of the brain. That isn’t the case. Endothelial cells have specific receptors that can be activated by cytokines. The endothelial cells then pass messages to the glial cells. In addition, circumventricular organs (specialized brain structures that connect the brain to the blood and cerebrospinal fluid) allow brain tissue to sample small amounts of immune molecules in the peripheral circulation. Also, cytokines in the blood that reach the meninges can enter the glymphatic system.
The inflammatory reflex connects the brain and the immune system. Inflammatory cytokines can be detected by the vagus nerve indicating that there is inflammation. The vagus nerve can carry a message from the brain to the spleen making it produce fewer cytokines and so return to a more standard state – an example of homeostasis.
The precise part of the brain activated when the bowel is inflamed was, in 2021, discovered to be the insula – an area that mediates the relationship between the brain and the body.
Autonomic nervous system balance
The autonomic nervous system (ANS) is the part of the nervous system that regulates the body’s automatic functions – processes that happen without conscious effort, such as heart rate, breathing, digestion, blood pressure, temperature regulation, and immune activity. It acts as a continuous monitoring and response system, constantly adjusting the body’s internal state to meet changing demands and maintain homeostasis.
The ANS has two main branches: the sympathetic nervous system (SNS) and the parasympathetic nervous system (PNS).
The sympathetic nervous system is responsible for mobilization and action. It prepares the body to deal with challenge or threat – the classic fight-or-flight response. When activated, it increases heart rate, raises blood pressure, redirects blood flow toward muscles, releases glucose for immediate energy use, sharpens attention, and temporarily suppresses non-essential functions such as digestion and tissue repair. It also activates inflammatory pathways and mobilizes immune cells to likely sites of injury, such as the skin and mucosal surfaces, preparing the body for possible infection following physical danger.
The parasympathetic nervous system has the opposite role. It supports recovery, restoration, and repair – often described as the rest-and-digest system. It slows heart rate, stimulates digestion, promotes nutrient absorption, supports tissue repair, and helps regulate inflammatory responses. Much of its activity is mediated by the vagus nerve, which carries signals between the brain and internal organs. The vagus nerve is central to what is known as the inflammatory reflex, through which the brain can detect inflammation in the body and dampen immune responses when inflammation is no longer helpful.
Health depends not on one branch dominating the other, but on flexibility and balance between the two systems. A healthy autonomic nervous system can rapidly shift into sympathetic activation when action is needed and then return efficiently to parasympathetic recovery once the challenge has passed. This flexibility is sometimes called autonomic resilience.
Problems arise when the sympathetic system becomes chronically dominant. Modern life often exposes people to ongoing low-level psychological stress – work pressures, financial worries, social comparison, loneliness, uncertainty, poor sleep, and information overload. Although these are not physical threats, the brain may interpret them as danger signals and maintain prolonged sympathetic activation.
When this happens, the body remains in a state of low-level physiological readiness. Digestion becomes less efficient, gut motility is altered, the gut microbiome may become disrupted, inflammatory cytokine production can increase, and cortisol regulation may become impaired. Over time this can contribute to chronic inflammation, immune dysregulation, fatigue, anxiety, poor concentration, disrupted sleep, and low mood.
Reduced parasympathetic activity, particularly reduced vagal tone, is associated with poorer emotional regulation and greater sensitivity to stress. People with lower vagal tone often show greater physiological reactivity to minor challenges and slower recovery after stress. This may partly explain why some clients appear ‘stuck’ in patterns of anxiety, hypervigilance, panic, or emotional exhaustion.
For hypnotherapists, this is clinically important. Many therapeutic approaches – guided relaxation, hypnosis, slow diaphragmatic breathing, mindfulness, and positive imagery – appear to work partly by shifting autonomic balance toward parasympathetic dominance. Slow breathing, in particular, stimulates vagal activity and improves heart rate variability, an important marker of autonomic flexibility.
In practical terms, helping clients regulate their autonomic nervous system may improve much more than stress levels. Better autonomic balance can support improved digestion, reduced inflammation, stronger immune regulation, clearer thinking, improved sleep, greater emotional stability, and increased resilience to future stressors.
From this perspective, hypnotherapy is not simply helping clients ‘relax’. It may help retrain the nervous system to move more flexibly between states of activation and recovery – restoring the balance that allows the brain, immune system, and gut to work together effectively.
The brain as an immune organ
The job of the immune system is to fight off pathogens and keep an individual safe. What if it could use a person’s brain to influence their behaviour as a way of keeping them safe? This it does in two ways: sickness behaviour and pathogen avoidance.
What happens when an individual has an infection or inflammation? The answer is sickness behaviour (as discussed earlier). In fact, the responses are very similar to those found with depression.
This kind of behaviour uses little energy, which can then be used for immune activation and fever. The behaviour reduces the risk for primitive humans of being hunted because they seek shelter out of the way of other people, and it reduces the risk of passing the infection on to other members of the tribe. That makes it a very useful defence mechanism.
Humans are also repelled by objects that are likely to contain lots of pathogens such as faeces and rotten food. This pathogen avoidance behaviour can prevent people from getting infected in the first place.
It’s also been found that people can identify other people who have some kind of infection. This could be by the smell of their sweat, or the way that they walk. Experiments have found some false positives, which is not too much of a problem in terms of becoming infected, but also some false negatives (ie missing the fact that the person is infected), which could lead to health issues. As a consequence, humans tend to be overprotective, and are likely to take extra precautions.
The brain
The brain was thought to be a responsive organ that took input from the senses and then responded appropriately. However, it’s now thought by many that the brain works as a predictive organ. It builds a model of the world and then guesses what’s going to happen next in any situation. It’s ready to respond to what it expects to happen much faster than it would be if it had to respond after an event occurred.
If events happen differently to the prediction, then the brain deals with the situation slower than it would have done otherwise. It then changes its model to allow for the ‘error’ in order to create a more accurate model of the world.
The brain gets messages from the outside world – exteroception – as well as from inside the body itself – interoception. External senses are very good. Internal senses are less precise. It’s suggested that the brain’s interpretation of the sensations it receives results in the experience of emotions. A person can experience as many or as few emotions as they have words or concepts to describe them. Many people believe that emotions are ‘prescriptions for action’ to keep the body in balance. Emotions are also goal directed to minimize uncertainty and maintain homeostasis in the body.
On the downside, over-predicting and attributing excessive salience to sensory data can lead to hallucinations and delusions. The opposite can result in a person feeling dissociation or detachment from their emotions, their body, or the world.
There’s evidence that short-term inflammation following an infection can alter the function of N-methyl-D-aspartate (NMDA) receptors in the brain, making it harder for the brain to update its model of the world. This can also lead to delusions and hallucinations.
People with chronic pain or fatigue may have higher levels of prediction errors when detecting messages from the body. This could lead to the brain believing that it’s still fighting an infection.
The brain and the immune system
One growing idea is that immunoception is the body’s ability to detect infection and the behaviours driven by those feelings. Like interoception generally, it’s not very exact.
How a person feels at any moment is a combination of bottom-up feelings, eg from an infection, and top-down thinking about things, and predicting (sometimes wrongly) the likely outcome.
When a person is stressed for any length of time, their immune system is activated.
A study on rats by Ader in the 1970s found that rats that were given an immunosuppressant injection and sugar flavoured water also showed an immunosuppressant response when they drank just sugar-flavoured water. It’s as if the brain and immune system were both predicting the response.
There is evidence that the brain can ‘remember’ inflammation in the bowel, and re-inflame it without the need for any external physical trigger.
Like the brain, the immune system is self-organizing and self-maintaining. It has its own model of the environment, which it can update as necessary by sensing and acting on changes in the microscopic environment. It may carry out immunoceptive inference, ie it provides predictions about, and acts on, sensory input about whether an antigen is ‘self’ or ‘non-self’.
Links between the brain and the immune system predict the environment and try to reduce uncertainty.
If the immune system becomes hypervigilant about attacks – hypersensitive – it can result in allergies and autoimmune disease. If the brain becomes hypervigilant, it can result in PTSD and phobias.
Lots of infections early in life can lead to the risk of mental health conditions later in life. In addition, stress early in life can lead to inflammation.
The hygiene hypothesis suggests that early exposure to certain microorganisms helps individuals develop a healthy immune system. However, our modern sanitized world doesn’t allow a person’s immune system to learn to differentiate good bacteria from hostile pathogens, or self from non-self. People are, therefore, more susceptible to allergies and autoimmune diseases.
Similarly, humans don’t face the kind of stress faced by our ancestors, and modern threats may lead to mental health issues.
There are a number of examples of the brain being able to affect the immune system. For example, if someone mistakes, say, a model flower for a real one, their immune system may respond as if it were a real flower, and they will quickly start suffering from hay fever.
Secondly, placebo drugs can have a positive effect on the body – even if the person knows it’s a placebo. The placebo is not having any impact on the body, but the mind thinks it is, and positive results can be seen.
Similarly, context can affect how much pain a person feels.
It’s also been found that looking at the faces of sick people can trigger inflammation in the body. In addition, anger comes with high levels of inflammatory markers in the blood in the short term. So do other negative emotions.
Psychoneuroimmunology is the study of the interactions among behavioural, neural, endocrine, and immune processes.
Gut microbiome
It used to be thought that all small organisms (bacteria, viruses, etc) were bad and needed to be killed. Some can influence behaviour. For example, the Toxoplasma parasite can infect mice, invading their brain and causing inflammation. It can also cause a change in the behaviour of a mouse, making it more likely to be caught and eaten by a cat. The parasite reproduces in a cat’s gut.
Another example is the rabies virus, which causes inflammation of the brain and spinal cord, leading to brain dysfunction and death. The rabies virus travels to the brain through the nerves after entering the body through a bite or broken skin. It changes a person’s behaviour, leading to aggression and biting, which spreads the disease.
On the other hand, penicillium, which is a fungus, led to the discovery of antibiotics, and is beneficial to the body.
It’s now recognized that the gut is full of bacteria, which are mostly beneficial to their host. Non-beneficial bacteria lead to food poisoning symptoms as the body tries to get rid of them. Current estimates suggest that around half the cells associated with the human body are microbial. The gut microbiome includes thousands of species of bacteria as well as viruses and fungi.
Beneficial gut microbes generally outcompete bad microbes (pathogens) for space and so keep the gut healthy. The majority of the gut microbes live in the colon (the main part of the large intestine). Around 60 percent of the faeces a person produces are microbia, although the exact figure depends on hydration and diet. An absent or unbalanced gut microbiome is called dysbiosis, which can have a significant effect on the mind and immune system. For example, gut dysbiosis can also lead to inflammation.
One role of gut microbes is to break down fibre in the diet and produce short-chain fatty acids (SCFAs) like butyrate, propionate, and acetate. These compounds have anti-inflammatory effects and can cross the blood-brain barrier, influencing brain function and behaviour. It’s hypothesized that the type of bacteria in a person’s microbiome can affect the types of food they like to eat.
Because the food a person eats can contain microbes of its own, there are more defensive immune cells in and around the gut than in blood and bone marrow.
There are four pathways between the gut and the brain. They are: neural, endocrine, metabolic, and immune. The vagus nerve has neuropod cells where it connects to the gut. These cells taste the environment of the gut and pass the information up the vagus nerve to the brain.
The types of body functions that the gut-brain axis (GBA) or connection affects include:
Behaviour
Cognitive function
Digestion
Food preferences and cravings
Food sensitivities and intolerances
Gut motility (muscle movements)
Hunger and satiety
Immunity
Metabolism
Mood
Pain sensitivity
Stress levels.
The gut does have its own ‘brain’, the enteric nervous system (ENS). It’s a network of neurons that controls the digestive system. It’s part of the autonomic nervous system, however, it can control gastrointestinal behaviour independently of central nervous system (CNS) input.
Mice without a microbiome in their gut behave differently to other mice. They are more stressed and produce higher levels of the mouse equivalent to cortisol, and produce lower levels of brain-derived neurotrophic factor (BDNF), which is important for learning and memory. Giving the mice probiotic bacteria was beneficial, but it only reduced stress if it was given in the first few weeks of life.
The composition of the microbiome of animals that have been stressed in early life is different from the microbiome of unstressed animals. Feeding the animals probiotics reduced their stress response. Also, cutting the vagus nerve removes a link between the gut and the brain, and removed the stress response.
Mice with no microbiome have reduced anxiety-like behaviour, but lack fear-related recall. They also have enlarged amygdalae. Mice also had an excess of myelination in the neurons in the pre-frontal cortex. These microbiome-free mice also tend to be loners, showing reduced social engagement.
Interestingly, transferring the microbiome from depressed humans into rats made the rats depressed!
In 2022 a study showed that pain sensing neurons in the gut can not only detect molecules produced by gut bacteria, but also produce molecules that regulate the types of bacteria around them.
Microbe-derived molecules can stimulate endocrine cells in the gut lining (enteroendocrine cells) to produce different hormones. These interact with the vagus nerve to influence hunger and eating preferences. Short-chain fatty acids can directly communicate with the brain by crossing the blood-brain barrier, as mentioned earlier.
Gut microbes can also produce the precursor molecules for neurotransmitters and neuromodulators, including GABA.
Psychological stress, such as anxiety and depression, can alter gut microbiota composition and increase intestinal permeability, allowing harmful substances to enter the bloodstream and trigger an immune response. They can also lead to gastrointestinal issues like irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD).
Research in 2022, by Kirsten Berding at al, found that eating a psychobiotic diet of prebiotic fibre, legumes, and fermented foods demonstrated a direct causal microbiome change driving reduced stress by 32 percent compared to a control group with a reduction of 17 percent. Prebiotic fibre included onions, leeks, garlic, cabbage, apples, asparagus, banana, oats, dark chocolate (cocoa), and barley. Legumes included lentils, chickpeas, kidney beans, and black beans Fermented foods included kimchi, sauerkraut, kefir, and kombucha. In this case, one serving of fermented foods was equivalent to one cup. A psychobiotic diet is a diet that aims to improve mental health by eating foods that support gut microbiome health.
The gut and the immune system
The gut is not just a digestive organ, it’s also the largest immune organ in the body. Gut bacteria influence immune cell development and response. Approximately 70-80 percent of immune cells reside in the gut-associated lymphoid tissue (GALT), making the gut a critical player in immune defence.
Gut bacteria help to train immune cells, teaching them to distinguish between harmless and harmful agents. Gut dysbiosis can disrupt this training process, leading to an overactive immune response and chronic inflammation.
Because of the link between the gut microbiome and the immune system, cytokines and immune cells can reach the brain.
Gut bacteria train the immune system through:
Immune cell development – the gut microbiome plays a key role in the development and maturation of immune cells, including T-cells, B-cells, and dendritic cells. These cells learn to distinguish between harmful pathogens and harmless substances, reducing the risk of autoimmune reactions.
Regulation of inflammation – a healthy gut microbiome produces anti-inflammatory compounds like SCFAs, which help regulate immune responses. Dysbiosis can lead to chronic inflammation, a root cause of many diseases.
Barrier function – the gut lining acts as a barrier, preventing harmful bacteria and toxins from entering the bloodstream. A healthy microbiome strengthens this barrier, while dysbiosis can lead to leaky gut syndrome, where toxins leak into the bloodstream and trigger immune responses.
The immune system protects the gut through:
Mucosal immunity – the gut is lined with a layer of mucus that contains immune cells and antibodies (Immunoglobulin A – IgA). This mucosal immune system helps neutralize pathogens and maintain a healthy balance of gut bacteria.
Pathogen defence – immune cells in the gut constantly monitor for harmful invaders. When pathogens are detected, the immune system mounts a targeted response to eliminate them.
The brain under attack
We’re unlikely to see people with psychosis (hallucinations and delusions), personality change, and uncontrollable movements, but these are symptoms of an autoimmune response that affects the brain. One example is anti-NMDA (N-methyl D-aspartate) receptor encephalitis (inflammation of the brain). The treatment is immunotherapy.
Other examples of diseases caused by autoimmune responses include multiple sclerosis (MS), which causes breakdown of the protective covering of nerves. There also seems to be a link between schizophrenia and autoimmune disease.
Psychotic disorders and autoimmune diseases seem to stem from a combination of infections, gut dysbiosis, and genetic susceptibility that leads to chronic infection. Having all of those conditions increases a person’s chances of developing a psychotic disorder and/or an autoimmune disease.
Depression
Some people with depression who are given anti-inflammatory drugs feel less depressed. These drugs include tumour necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). The drugs that block the cytokines for IL-12 and IL-23 help some people with psoriatic arthritis clear up the psoriasis. On the other hand, giving people interferon-α (IFN-α), a protein produced by the immune system that causes inflammation, made some recipients feel depressed.
It seems that around a third of people diagnosed with major depressive disorder (MDD) are in remission with antidepressants, around a third are helped, and the final third are unaffected. Around a quarter of people with depression have inflamed depression. Their blood has mildly raised levels of C-reactive protein (CRP), which is an inflammatory marker, indicating low-level chronic inflammation. They also have more peripheral inflammation, and have raised numbers of innate and adaptive immune cells in their blood. Inflammation is more associated with some depression symptoms than others, including, greater fatigue, need for sleep, changes in appetite, low energy, low concentration, slowness of mind and body, and anhedonia (a lack of interest, enjoyment, or pleasure from life’s experiences). The symptoms associated with depression are very similar to the symptoms associated with many other illnesses such as influenza or Covid – typical sickness behaviour.
Across the world, what one thing could have a massive impact on reducing depression?
The answer is cement!
That’s according to Ed Conway in his book, Material World: A Substantial Story of Our Past and Future. When Mexico gave families cement to pave over dirt floors parasitic infections dropped by 78%, the number of children with diarrhoea dropped by half, and those with anaemia dropped four fifths. In addition, children did better at school, and their mothers became happier and less depressed.
Nerves can sense the state of the immune system and communicate it to the brain. Inflammatory cytokines travel in the blood to the brain where they either interact with the blood-brain barrier or enter the brains. Immune cells can travel to the brain and influence behaviour. Microglia in the brain can be activated by any of these pathways and create more cytokines.
Normal sickness behaviour is usually short lived, whereas depression lasts much longer.
Evidence often shows that inflammation precedes the onset of depression. The amino acid, tryptophan, usually breaks down to produce the neurotransmitter serotonin. Cytokines activate an enzyme that breaks down tryptophan into quinolinic acid (the kynurenine pathway), which has a depressive and even toxic effect on the brain.
Some cytokines and chemicals called reactive oxygen species (ROS) can reduce the synthesis and release of dopamine, making people less motivated to do anything.
Inflammation also slows down neurogenesis (the creation of new neurons) in the hippocampus.
When people have inflammation, there is an increase in activity in the insula, a brain area that is aware of what’s happening in our body (interoception).
People with depression often have an overactive amygdala, particularly in response to negative stimuli. Interferon-α triggers increased activity in the amygdala in response to negative stimuli before people get depression. Minor threats are treated as major ones. Anti-inflammatory drugs reduce amygdala activity. So, inflammation nudges us towards being more sensitive to negative information. For some this can lead to depression.
According to research by Bei Wu et al (2025) published in BMC Oral Health, depression was associated with a reduced diversity of microbes in the mouth.
Minocycline is a drug that targets inflammation in the brain, and seems to help those people with inflammatory depression. It can cross the blood-brain barrier and stops microglia from becoming pro-inflammatory, and dampens down the kynurenine pathway (which breaks down tryptophan into a toxic product rather than serotonin).
The severity of traumatic events in childhood – adverse childhood experiences (ACE) – seems to correspond to a lack of response to standard antidepressants, and glucocorticoid resistance leading to inflammation and high cortisol levels.
It seems probable that depression can cause inflammation, and inflammation can cause depression.
Blue Monday in 2026 occurred on 19 January. It’s usually the third Monday in January in any year, and is meant to be the most depressing day of the year. With the Christmas and New Year celebrations now behind us, and, in the northern hemisphere, the days being cold and dark, people can feel sad, and they lack energy, motivation, and enthusiasm.
Is it really a scientifically measured event? Is it really the most depressing day of the year for most people? The answer is, of course no. Back in 2005 Sky Travel, a UK travel company was looking for a way to sell holidays. They issued a press release claiming to have calculated the most depressing day of the year. And what better way to cheer yourselves up than to book a holiday?!?!
On the plus side, the idea of Blue Monday does highlight the need for self-care and support for all of us, as well as the need for mental health awareness generally.
Stress
Stress is the alteration of the body in response to a dangerous situation being recognized by the mind. When a person is stressed, their adrenal glands produce adrenalin, which causes glucose to be released from the liver that is then transported in the blood to the muscles. Their heart rate and blood pressure increase, their mouth dries, and their bowels prepare to empty. Their mind becomes alert and hyper-focused. Their immune system activates and immune cells from bone marrow, lymph nodes, and the spleen travel in the blood to barrier surfaces such as the skin, where they can be ready to deal with pathogen invaders. Stress hormones can alter gut motility, reduce blood flow to the digestive system, and disrupt the balance of gut bacteria. This can lead to symptoms like bloating, cramping, and constipation. Over time, chronic stress can alter the composition of gut bacteria, leading to dysbiosis and inflammation. Over time, diverting resources away from non-essential functions like digestion and immunity can lead to immune dysregulation and increased inflammation.
Noradrenalin is also produced, which stimulates inflammatory pathways within certain immune cells, which then secrete inflammatory cytokines. This is the short-term fight-or-flight response, and is good.
High chronic levels of cortisol can suppress some immune functions but also contribute to inflammatory dysregulation via glucocorticoid resistance. Prolonged cortisol exposure can weaken the immune system, making the body more susceptible to infections.
Stress mobilizes large numbers of neutrophils that travel to peripheral tissues. Neutrophils can engulf bacteria, or spray them with antimicrobial molecules, or entrap them in a net of proteins.
Chronic social stress increases antibacterial immunity, but decreases antiviral immunity.
Many people experience continual low levels of stress in their everyday lives, and that has implications for their defence systems and their health. While their immune system adapts to fight bacteria, it is less good at fighting viruses. Chronic stress suppresses natural killer cells that identify cells infected with viruses and kills them. Natural killer cells also detect and destroy cancer cells. That’s why long-term stress is associated with cancer progression and recurrence. Because chronic stress weakens the immune system, viruses lying dormant can reactivate, eg the varicella-zoster virus, which causes shingles around a nerve ending.
The extra antibacterial immune cells are pro-inflammatory, and they become less responsive. In addition, stress can prime microglia in the brain to become more inflammatory.
Chronic psychosocial stress (eg divorce, family death, prolonged illness, natural catastrophe, friendships, difficulties, etc) affects the gut microbiome leading to inflammation. Loneliness is psychosocial stress, and chronic loneliness has health risks comparable to major established risk factors, including smoking in some analyses. It’s also been found to cause depression and suicide, is contagious, and affects more-and-more people. The body sees prolonged isolation and social rejection as a threat to survival.
All of these conditions can lead to mental health conditions, dementia, and heart disease.
Stress is also linked to allergies (eg eczema) and autoimmune disease.
There is some evidence that the link between stress and PTSD may be inflammation.
Inflammation affects how the brain processes rewards. People are less likely to strive to seek rewarding things, and sensitivity to punishment goes up.
Dementia
The immune system can play a part in dementia. Pneumonia and urinary infections are very often the cause of the inflammation. A 2010 study of 1500 people found that those with Alzheimer’s disease tended to have raised inflammatory cytokine levels in their blood.
Observational analyses suggest that the shingles vaccine reduces the risk of developing dementia by around 20 percent This is according to analysis of data from The National Health Service in Wales, which gave shingles vaccinations in 2013 to people over 80 years old.
Researchers from the University of Southampton in 2016 found a link between systemic inflammation and dementia, in particular those people with gum inflammation (periodontitis) had a sixfold increased risk of developing Alzheimer’s.
Alzheimer’s patients have clumps of proteins (called amyloid plaques) made up of amyloid proteins. They also have deposits of tau proteins aggregated together. Tau proteins usually contribute to the structure of nerves in the brain.
A Boston study in 2016 found that clumps of amyloid beta protein are able to entrap bacteria, and have antiviral and antifungal properties. The fact that these plaques appear in Alzheimer’s could be as a result of an excessive and prolonged inflammatory response in the brain.
Microglia become primed when stimulated by systemic inflammation, and react more aggressively, producing more inflammation the next time they are exposed to inflammatory stimuli. This neuroinflammation results in the destruction of neurons.
Additionally, synapses are coated in complement proteins, which the microglia react to by ‘eating’ the synapses.
It has been argued by some researchers that Alzheimer’s is in fact an autoimmune disease.
Clinical implications for hypnotherapists
Understanding the connections between the brain, the immune system, and the digestive system including its microbiome, enables hypnotherapists to offer targeted interventions beyond generic relaxation techniques. By addressing the brain-immune-gut axis, they can help clients manage stress-related conditions more effectively.
Dietary interventions:
Psychobiotic foods – incorporate probiotic-rich foods (ie ones that contain beneficial bacteria and are often created through fermentation) like yogurt, kefir, sauerkraut, and kimchi, as well as prebiotic foods (ie non-digestible fibres that nourish beneficial bacteria in the gut) like garlic, onions, bananas, and asparagus. See page 39 for a longer list of foods.
Fibre-rich foods – aim for at least 25-30 grams of fibre per day from fruits, vegetables, whole grains, and legumes. Fibre feeds beneficial gut bacteria and promotes the production of SCFAs. It’s suggested that people should try to eat 30 different plants in their diet each week.
Anti-inflammatory foods – include foods rich in omega-3 fatty acids (eg salmon, walnuts) and antioxidants (eg berries, leafy greens) to reduce inflammation.
Avoid ultra-processed foods (UPFs) – they may negatively affect microbial diversity and promote inflammation.
Managing stress:
Mindfulness and meditation along with deep breathing or yoga have been shown to reduce stress and boost immune function. For example, studies have found that meditation increases the activity of natural killer cells, which play a key role in defending against viruses and cancer.
Laughter and positive social interactions can enhance immune function by reducing stress hormones and increasing the production of immune-boosting compounds like endorphins.
On the other hand, poverty and loneliness lead to chronic stress and chronic inflammation. These are due to poor diet, poor sleep, and poor movement, and the body’s perception of social isolation and perceived low social status as a threat to life.
Regular physical activity has been shown to improve gut microbiome diversity and boost immune function. The composition of a person’s gut microbiome can influence how keen they are to exercise. Some gut microbes produce fatty acid amides (FAA), which binds to the cannabinoid receptor 1 (CB1) found on specific nerves in the gut. These nerves reach the brain where, when stimulated, they result in a surge of dopamine during exercise.
Exercise has lots of other benefits for the body. For example, running can help people with depression. Dance seems to be particularly beneficial for the body. Exercise can reduce inflammation, whereas sitting down can be inflammatory.
A 2021 study in Texas found that, in mice, stem cells that give rise to lymphocytes have mechanosensitive receptors that activate when the mouse is running. So, the mouse needs to run in order to create these immune cells.
Although exercise can cause inflammation, long-term exercise is anti-inflammatory. The World Health Organization (WHO) recommends 150 minutes of moderate exercise per week. Exercising in nature seems to be particularly good for people.
Sleep hygiene – prioritize sleep by maintaining a consistent sleep schedule, creating a relaxing bedtime routine, and avoiding screens before bed. Sleep is essential for immune regulation and mental wellbeing.
Sleep deprivation is bad for the immune system. One night of just four hours sleep reduced measured natural killer cells (the ones that destroy cells infected with viruses and cancerous cells) activity. Sleep loss also increases body-wide chronic inflammation.
Poor sleep is associated with low microbial diversity in the gut.
Research published in 2025 by Fatema Al-Rashed et al found that even a single night of sleep deprivation can alter immune cell profiles to resemble those seen in obesity, a condition linked to chronic inflammation. It found that sleep-deprived people had increased levels of non-classical monocytes – the immune cells associated with inflammatory responses.
Lifestyle changes:
Limit antibiotic use – antibiotics can disrupt the gut microbiome, so use them only when necessary.
Stay hydrated – drinking plenty of water supports digestion and helps maintain the mucosal lining of the gut.
An area that readers might like to find out more about is the hypothalamic-pituitary-adrenal axis (there will be a post about this in the future).
Conclusion
Ultra-processed food, inadequate exercise, disrupted sleep, and the loss of healthy gut bacteria have an inflammatory effect on the body and can lead to an unbalanced defence system. Chronic inflammation drives poor mental and physical health in the medium term. In the long term it can lead to heart attacks and strokes (atherosclerotic disease), diabetes and obesity (metabolic disease), dementia (neurodegenerative disease), and cancer. It’s this inflammation that can lead to the problems that some of the clients we see are experiencing. And that’s because the immune system influences our thoughts and emotions, and, of course, our thoughts can directly change the state of our immune system. Hypnotherapists can offer clients a science-backed path to resilience.
References:
https://en.wikipedia.org/wiki/Ren%C3%A9_Descartes
https://www.betterhealth.vic.gov.au/health/conditionsandtreatments/immune-system
https://my.clevelandclinic.org/health/body/the-gut-brain-connection
https://link.springer.com/referenceworkentry/10.1007/978-1-4419-1005-9_837
https://www.nature.com/articles/s41380-022-01817-y
Lyman, M. The Immune Mind: The New Science of Health. ISBN-10: 191170916X.
https://academic.oup.com/jimmunol/advance-article/doi/10.1093/jimmun/vkae016/8037869
https://bsd.biomedcentral.com/articles/10.1186/s13293-023-00495-x
https://bmcoralhealth.biomedcentral.com/articles/10.1186/s12903-025-06274-x