Answered: Why stress leads to gastrointestinal problems

Erwin van den Burg
14 januari 2025

Gastrointestinal problems are among the most common symptoms of stress. Have you ever wondered why you feel a knot in your stomach while being in a stressful meeting? Or why you have to visit the toilet urgently after an argument? Scientists know why: because of the powerful brain-gut connection.

Common stress-related gastrointestinal problems

Stress can have pronounced effects on your digestive system. There is quite an extensive list of gastrointestinal symptoms and conditions that can be attributed to stress. Some of these are:

  • Diarrhea
  • Constipation
  • Stomach cramps and aches
  • Lower abdominal pain
  • Indigestion
  • Unnatural hunger or loss of appetite
  • Nausea
  • Irritable Bowel Syndrome
  • Peptic ulcers

The brain-gut connection

There is a biological basis underlying the development of one or more of these symptoms during stress. This is the strong connection between the brain, where stress reactions begin, and the gastrointestinal system. To put it briefly, the gut is full of neurons, just like the brain. It contains the largest area of nerves and neurons outside the brain. Some even call it the “second brain”, but its official name is “enteric nervous system”. And these two brains communicate with each other.

The brain-gut connection. The brain and the gut communicate with each other via the vagus nerve (part of the parasympathetic nervous system and the sympathetic nervous system (not shown). Signaling occurs from the brain to the gut and vice versa. The enteric nervous system is also involved and is a "second brain" in our body. The lining of the gut separates the gut content with food, bacterial products and microbiota (bacteria) from the body. Microbiota signal via the gut, enteric nervous system and vagus nerve to the brain, and can influence stress sensitivity and mood. Modified from Natale, Ryskalin, Morucci, Lazzeri, Frati and Fornai, CC BY 4.0 via Wikimedia Commons.

The connections are taken care of by the sympathetic and parasympathetic nervous systems. The sympathetic nervous system is the activator of many bodily functions. As such, it activates the fast stress reaction, leading to the production of adrenaline (norepinephrine) by the adrenal glands. The parasympathetic nervous system calms things down. Activation of the parasympathetic nervous system, for instance by breathing exercises, reduces stress.

There is thus a clear biological relationship between the brain, the gastrointestinal system, and stress. This relationship is the basis of the gastrointestinal symptoms you may experience during stress.

Gastrointestinal stress reactions

Stress has important effects on motility of the gut. The upper gut, including the stomach and small intestine, exhibits marked reduced transit. Biologists believe that this may be an evolutionary defense mechanism to promote vomiting and reduce feeding, which is found in humans and animals alike. Conversely, stress increases the motility of the large bowel, and thus increases stool output and transit speed. This may be a defense mechanism to eliminate toxins or harmful bacteria and viruses.

Gastrointestinal problems are mediated by the stress hormone CRF

These changes are brought about by a hormone called corticotropin-releasing factor (CRF). CRF is released from nerve cells in the hypothalamus of the brain. These nerve cells release the hormone through long projections into other parts of the brain. One of these is the locus coeruleus in the brainstem. This is where arousal (such as during stress) and sympathetic and parasympathetic changes are mediated.

CRF can also be produced and released locally by cells in the intestines. These cells can be neurons of the enteric nervous system or cells of the immune system. CRF can activate specific cells of the immune cells known as mast cells. They will release molecules that will normally fight off bacteria or viruses invading the body, but can also increase the motility of the gut, so that the threatening bacteria and viruses wash out more quickly. This goes hand in hand with reduced water absorption, making the transit faster and resulting in diarrhea and lower abdominal pain. Reduced water absorption is mediated by the parasympathetic nervous system.

Brain areas involved in stress responses

The hypothalamus and locus coeruleus are two of the primary brain regions that are activated during stress. The hypothalamus is activated by the amygdala, the brain’s emotional center controlling fear and aggression, and the locus coeruleus. The hypothalamus and locus coeruleus actually stimulate each other. This mutual activation may create a vicious cycle, in which the activation of one region stimulates the other, which in turn stimulates the first even stronger.

Brain regions involved in stress responses. The amygdala (red) is the brain's center of fear and activates the hypothalamus (blue) to produce the stresshormone CRF. The locus coeruleus (green) is an important alert center during stress and produces noradrenaline (Nor in the figure). Noradrenaline stimulates the production of CRF in the hypothalamus, and CRF stimulates the prodcution of noradrenaline in the locus coeruleus. CRF and noradrenaline exert important effects on the gastrointestinal system.


Link between stress responses and gastrointestinal problems

The locus coeruleus and the hypothalamus are both important for stress reactions and gastrointestinal functioning. The locus coeruleus releases noradrenaline (norepinephrine) and activates the sympathetic nervous system during stress, initiating the fight-or-flight reaction. Noradrenaline increases alertness and also stimulates the motility of the lower part of the gastrointestinal tract.

CRF release from the hypothalamus is the first step in the activation of the hypothalamic-pituitary-adrenal axis (HPA axis) involved in the stress response. The end product of the HPA axis is the stress hormone cortisol. CRF, as mentioned earlier, inhibits motility of the upper part of the gastrointestinal tract, and enhances motility of the lower part.

The stress hormones CRF and noradrenaline do not only serve to elicit the typical stress reactions in the body to activate the sympathetic nervous system and the HPA axis, leading to the release of adrenaline (epinephrine) and cortisol from the adrenal glands. They also change motility of the gastrointestinal tract. These changes may therefore be considered to be part of stress responses.

On the one hand, a lack of appetite, one of the symptoms of gastrointestinal problems, will save time to seek for food and to prepare a meal. Because of this, you have more time to deal with the problem that gives you stress. Also, the nausea and diarrhea that can occur during stress may have evolved from biological mechanisms to get rid of toxins (toxins can also be stressors, as they may disturb homeostasis, or equilibrium, in the body), or dangerous bacteria or viruses.

Stress and gastrointestinal disease

Two of the major causes of uncomfortable or painful intestinal symptoms are irritable bowel syndrome (IBS) and indigestion problems (known as dyspepsia). IBS occurs in approximately 12% of people worldwide. Dyspepsia is also very common.

In both IBS and dyspepsia, symptoms occur that are similar to those observed during stress. In IBS, the motility of the colon is generally increased. In dyspepsia, the stomach doesn’t empty so easily, reducing food intake.

In IBS patients, the gastrointestinal system is more sensitive to stress than in people without the disease. Therefore, the motility changes induced by CRF are more pronounced. This can result in diarrhea and intestinal cramps.

IBS in general worsens by stress. IBS in people who are not under stress tends to resolve all by itself. However, when IBS patients are suffering from stress, symptoms persist.

Conversely, IBS can be triggered by stress, especially by stressful events early in life such as bereavement or abuse.

Peptic ulcers

It is well known that stress can cause ulcers in the stomach. However, it is still a mystery how stress does it. Although some researchers blame cortisol, which could affect the lining of the stomach, this has not yet been proven.

A correlation has been found between dopamine in the brain and risk of getting an ulcer. Dopamine is a messenger molecule, very similar to adrenaline and noradrenaline. It is involved in motivation and experiencing pleasure. During stress, the dopamine system is inhibited. Stressed people therefore experience less joy in their lives. People with Parkinson's disease produce almost no dopamine, and stomach ulcers are relatively common in these patients. People who are schizophrenic have more dopamine, but almost never an ulcer. Animals in the laboratory, like Parkinson's patients, get more stomach ulcers when their dopamine production is stopped, and fewer when the receptors for dopamine are activated.

These studies do not yet conclusively prove that dopamine in the brain does indeed play a role in the development of peptic ulcers. Nor do they show how dopamine might do so. More research is needed to find out precisely how stress leads to the formation of ulcers in the stomach.

Inflammatory bowel disease

Inflammatory bowel disease, abbreviated IBD, is a group of chronic inflammations of the gastrointestinal tract. The best known of these are Crohn's disease and colitis. Symptoms include diarrhea, blood or mucus in the stool, abdominal pain and weight loss.

The causes of Crohn's disease and colitis have not yet been unambiguously determined. Studies in laboratory animals suggest that stress is a risk factor for both conditions. Although there is also a link between stress and IBD in humans, it is not clear whether stress causes IBD, or is a consequence of the disease. Some researchers attribute an important role to CRF. Much research is currently being done worldwide to identify the molecules that cause IBD.

The brain-gut axis extended: microbiota

In the communication between the brain and the gut, the bacteria living in the gut play an important role. They can modify information about the status of the intestines to the brain via the vagus nerve, running from the gut up to the brain. Odd as it may seem, gut bacteria (collectively referred to as microbiota) influence how the brain works, and can change our social behavior and mood!

Chronic stress can disturb the balance of the intestinal microbiota, favoring the growth of some strain at the expense of others. How this happens is not precisely known. However, it may be that it is the consequence of an imbalance of the immune system, leading to gastrointestinal and more general inflammation.

Conversely, the microbiota composition in the gut influences how you respond to stress. This is because of two reasons.

First, microbiota are required for normal brain development and brain function in adulthood. If you have the “wrong” bacteria, your brain will not develop and work optimally. This may change your emotionality (like anxiety and depression) and your perception of stressful events. Some clinicians and scientists go as far as to say that future treatment of psychiatric disorders (and perhaps also the consequences of chronic stress) should include an analysis of microbiota composition and even replacement of the bacteria living in the gut!

Second, gut bacteria communicate directly with the brain. They do this through the vagus nerve, the enteric nervous system of the intestines, serotonin (a messenger molecule of neurons), the immune system and products they make themselves. They inform the brain about the health, gut content (food)  and functionality of the intestinal system.

The study of microbiota in relation to stress and mental health is relatively new, but booming! Scientists still have not figured out completely how the bacteria in the intestines influence stress and vice versa. This is because most knowledge about microbiota comes from studies in laboratory animals. Clinicians are now in the process of understanding how microbiota work in humans.

Stress management to improve gastrointestinal problems

To reduce gastrointestinal problems that are caused by stress, you can try to use the more common techniques to reduce stress. These include breathing exercises, physical exercises, yoga and meditation. However, are there specific stress management techniques to reduce gastrointestinal problems specifically?

The answer to this question is yes. Building on the idea that microbiota influence your perception of stressful situations, it seems fair to say that gut bacteria determine your stress sensitivity. The concept that scientists and clinicians are trying to bring forward nowadays is that a healthy composition of microbiota in the gut will reduce your stress sensitivity. In other words: you will react less strongly during times of stress, and therefore your gastrointestinal and other stress-related problems will also be less severe.

Bacteria reach your gut via the mouth with the food. This is one of the reasons that eating healthy food is so important. An equilibrated meal with vegetables and fruit does absolute wonders for your microbiota. Not only will you ingest the “good” bacteria, but you will also nourish the ones already living in your intestines at the expense of the "bad" ones.

Another strategy to reduce gastrointestinal problems is by using a neurologic approach. This may be especially useful if you are suffering from IBS or dyspepsia. Emotional distress is very common if you happen to have one of these and related diseases, especially if the disease prompts you to seek medical treatment. For example, anxiety and depression occur in 40% of IBS and dyspepsia patients that need professional help to cure the disease. Accordingly, psychotherapy and hypnosis seem to be helpful to reduce IBS and dyspeptic symptoms. Also, tricyclic antidepressants appear to work, even in low doses. They reduce the brain’s response to intestinal pain during stress.

Now that you understand that stress influences the bacteria in your gut, and that these bacteria influence stress sensitivity and stress responses, you will understand that nurturing the “good” bacteria in your gastrointestinal system is important to reduce stress. We will therefore continue to publish articles on stress, nutrition and the gastrointestinal system, microbiota included.