Jack Harley, Therapeutic Neuroscience at Oxford University
reviewed by Dr Michael Yapko
Tuesday, March 17, 2020
Jack Harley, Therapeutic Neuroscience at Oxford University
Tuesday, March 17, 2020

The Mind-Gut Connection: How the Gut and Brain Work Together


Have you ever felt ‘butterflies in your stomach’ when nervous? According to science, there is a very real connection between gut and mind. This ‘gut-brain’ explains how stress and anxiety can contribute to IBS, and also how the food you eat can impact your mental health. By understanding the mind-gut connection, science can help improve your mental and gastrointestinal health.

The gut-brain axis

The gut-brain axis is the two-way communication system between the brain and belly. This axis maintains the body’s state of steady functioning known as homeostasis. (1) Several components make up the gut-brain axis:

  • The brain
  • The nerves surrounding the gut (enteric nervous system)
  • The vagus nerve
  • Gut bacteria (the microbiome)
  • Hormones such as serotonin (2)

What is the Enteric Nervous System?

The gut is encased by 100 million neurons, called the enteric nervous system (ENS). This ‘second brain’ controls the processes of digestion including motility – the movement of food through the intestines - and the secretion of fluids. The ENS network extends from the esophagus down through the intestines to the anus.

This ‘second brain’ is in constant contact with the brain in our head and plays an important role in psychiatric and GI diseases. The vagus nerve is one of the largest nerves that sends signals from the brain to the gut and vice-versa.

Abnormal brain-gut communication can interfere with the body’s ability to maintain homeostasis, and lead to disease. Disruption to the ENS may lead to mental health problems such as depression or anxiety. Conversely, thoughts or emotions of stress and anxiety can elicit exaggerated gut responses. (3, 4, 5)

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Anxiety and bowel issues

The link between gut and brain explains how stressful situations – such as giving a presentation or sitting an exam – may cause nausea and abdominal pain. Stress, anxiety and other psychological factors influence the passage of material in the GI tract and cause symptoms of irritable bowel syndrome (IBS). There are several theories explaining how this, suggesting stress may cause symptoms by:

  • Heightening sensitivity to pain (visceral hypersensitivity)
  • Activating the immune system causing inflammation
  • Influencing microbiota
  • Altering motility (the speed of material through the intestines) (6, 7)

Irritable bowel syndrome: gut-brain dysfunction

A common condition arising from gut-brain miscommunication is irritable bowel syndrome (IBS), affecting 1 in 9 people globally. (8) IBS is a gastrointestinal disorder of abdominal pain associated with either constipation or diarrhea. Common symptoms of IBS include:

  • Abdominal pain and bloating
  • Bloating
  • Constipation or diarrhea
  • Nausea
  • Wind (9, 10)

Although IBS produces physical symptoms, several scientific studies have shown mental health conditions affect the severity of IBS. This implies the gut-brain connection is real and relevant to IBS. For example:

  • IBS is more common in patients with pre-existing psychiatric illnesses such as depression or anxiety. (11)
  • Symptoms of IBS worsen during times of heightened stress or anxiety. (12, 13)
  • IBS symptoms improve with psychological therapies such as hypnotherapy, cognitive-behavioral therapy (CBT) and mindfulness meditation. (14)

The ENS: An opportunity for therapy

The ENS-brain connection explains the effectiveness of antidepressants and mind-body therapies such as hypnotherapy and cognitive-behavioral therapy (CBT) for bowel disorders such as IBS. Essentially, the two brains ‘talk’ to each other and psychological treatments can target both at once.

When gastroenterologists prescribe antidepressants or psychological treatments, it is not because symptoms are ‘all in the head’ of the patient, but because these medications may impart benefits to the ENS neurons in the gut. (15)

Psychological therapies for bowel disorders

Psychological and mind-body therapies that have been shown in clinical trials to improve symptoms of IBS include:

  • Gut-directed hypnotherapy: following hypnotic induction, the patient is guided through suggestive imagery to visualize their gut as a series of tubes with fast-flowing contents, improving symptoms of IBS. (16)
  • Mindfulness meditation: in this practice, based on Buddhist tradition, the patient is guided to bring their awareness to the present moment and accept physical sensations being experienced. This has been shown to improve symptoms of IBS. (17)
  • Cognitive-behavioral therapy (CBT): Negative beliefs and appraisals of IBS symptoms and unhelpful thought patterns are challenged, to reduce perceptions and physical symptoms of IBS. (18)

How could a psychologist or hypnotherapist help with a gut problem?

Talk therapies such as cognitive-behavioral therapy (CBT) and hypnotherapy have been shown to improve GI symptoms and are thought to work by:

  • Improving vagus nerve signals
  • Reducing sensitivity to gut pain
  • Altering conscious responses to GI sensations (17, 19, 20)

What groups of GI patients might benefit from psychological treatments?

Certain groups of GI patients may be particularly suitable for psychological treatments. These include:

  • Patients with ‘functional’ GI symptoms (not explained by examinable damage or disease of the intestines) who have not responded to prior treatments.
  • Patients who experience worse symptoms during stressful periods
  • Patients who prefer non-drug treatment
  • All patients suffering from chronic and distressing GI symptoms, such as bloating and abdominal pain. (21, 22)

Neurotransmitters – another opportunity for therapy

Neurotransmitters, small hormones use for cell-to-cell communication are found in both the brain and the gut and important in the gut-brain axis. Serotonin (5-HT), is an important neurotransmitter associated with feelings of happiness and found in large amounts in the gut. Serotonin plays a role in digesting, controlling motility and the secretion of fluids in the intestines. (23)

Interestingly, levels of serotonin in people with IBS differ based on whether symptoms of constipation or diarrhea are present. Patients with diarrhea and IBS show higher circulating levels of serotonin after consuming a meal than those with constipation. This difference has led researchers to create IBS medications that act on specific serotonin receptors:

  • Alosetron (Lotronex) is a drug that blocks the serotonin receptor to improve symptoms of diarrhea.
  • Tegaserod (Zelnorm) stimulates this receptor to treat constipation.

This example shows how knowledge of the gut-brain axis is progressing the development of new treatments for IBS. (24, 25, 26)

The gut affects the brain, too

Not only does the brain affect the gut, but increasing research shows gut health can influence the brain. Unusual distributions of bacteria in the gut can lead to seemingly unrelated conditions such as autism spectrum disorder, and schizophrenia. (27)

The microbiome

There are trillions of microbes living in the GI tract, collectively known as the microbiome. When digesting fiber, these microbes produce short-chain fatty acids which can have effects on the brain. This is because many of these compounds are neuroactive, and can cross the blood-brain barrier.

An oversupply of pathogenic (harmful) bacteria in the gut can result in an overactive immune system, leading to inflammation and affecting the central nervous system. This inflammation can even lead to depression. Interestingly, probiotics may reduce depression by preventing the release of inflammatory signals called ‘cytokines’ into the body. (28, 29)

The microbiome at risk

The two above states of unhealthy microbe constituency are examples of ‘dysbiosis’ and are associated with many diseases. The key to maintaining a healthy microbiome is a healthy diet rich in fiber from fruits and vegetables. This helps to develop a diverse ecosystem of microbes that perform many functions and can replace each other’s roles if necessary. By contrast, an unhealthy diet deficient in plant-based products may lead to a lack of microbe diversity and disease. (30, 31)

The microbiome in brain disease

Schizophrenia, bipolar disorder, and Parkinson’s disease are linked with changes in the microbiome. Alterations in the normal, healthy balance of bacteria may cause the immune system to overreact, leading to inflammation and brain diseases. One study showed that patients with Parkinson’s disease had lower levels of one type of microbe, Prevotellaceae, and higher levels of another, Enterobacteriaceae compared to healthy controls. This suggests diet may play a role in protecting against Parkinson’s disease. (32)

Probiotics and brain health

Probiotics are live bacteria that impart health benefits. Research has shown some probiotics can improve the microbiome and benefit the brain, reducing symptoms of anxiety and depression.

A small study showed a probiotic containing Bifidobacterium longum significantly improved symptoms of depression over six weeks. Probiotics such as Bifidobacterium and Lactobacillus, found in yogurt, have been shown to improve mood and reduce anxiety. (33, 34)

However, a large meta-study of over 1500 patients from 14 studies showed that only 3 of trials showed probiotics improved symptoms of anxiety. This was much lower than for non-probiotic interventions, suggesting more work is needed to clarify the benefit of probiotics for anxiety. (35)

Prebiotics and brain health

Unlike probiotics, prebiotics do not contain a live organism. Prebiotics are fibers that are fermented by microbes, and may also influence brain health. One study showed three-weeks treatment with a prebiotic galactooligosaccharides reduced levels of cortisol, a ‘stress’ hormone. Other fermented products such as kefir, kambucha, and kimchi may also improve mental wellbeing, however, further research is needed.  (36)  

What are psychobiotics?

Psychobiotics is a term for live bacteria that confer benefits to mental health. These are probiotics, most commonly of Bifidobacterium and Lactobacillus families, or prebiotics that protect against diseases such as depression and schizophrenia. Psychobiotics influence the gut-brain axis via the spinal cord, vagus nerve and endocrine (hormonal) systems. (37)

Foods that improve the gut-brain axis

Recently, certain food groups have been shown to improve gut-brain functioning. Many of these contain psychobiotic compounds, and include:

  • Omega-3 fats: Found in oily fish and flaxseed, have been shown to improve microbiome diversity in adolescence and adulthood. This reduces the risk of brain disorders such as schizophrenia and depression.
  • Fermented milk products: Suchas various probiotic strains, found in yogurt and cheese. These have been shown to modulate brain activity
  • Fiber-rich foods: Such as fruits and vegetables, whole grains and nuts. These contain prebiotic fibers that reduce cortisol levels and alter emotional bias.
  • Cocoa: Found in chocolate products, has been shown to act as a prebiotic and probiotic and increase levels of Bifidobacteria and Lactobacilli microbes. Cocoa is rich in polyphenols, beneficial to the microbiome. (38, 39)

Autism and GI problems

Australian researchers recently found that a single gene causes both autism and gut problems. This helps explains why autism is accompanied by GI issues in 90% of cases. The brain and the GI tract share many of the same neurons, and the newly discovered mutation affects communication in the brain causing autism as well as:

  • Gut contractions
  • The density of neurons in the small intestine
  • Motility – the speed of transit of food through the intestine

This research further highlights the intimate connection between the brain and the gut. (40)

How gut bacteria can lower stress

Several avenues of research have shown how crucial gut bacteria are to our mental health. In 2004, Japanese scientists showed that gut bacteria influence stress in mice models. Mice that were kept in a ‘germ-free’ environment, without exposure to microbes in their bodies, showed greater fluctuations in the adrenal hormone corticosterone – associated with greater stress. When the researchers then administered the mice with Lactobacillus the mice showed lower levels of stress. This implies gut bacteria are crucial for reducing stress. (41)

What’s more, Chinese scientists showed gut bacteria from depressed patients could be transplanted into ‘germ-free’ mice and induce depressive behaviors. This demonstrates that ‘depressed’ microbiomes may even apply between species. (42)

On a broader scale, population-based studies from as recently as in 2019 have shown differences in the microbiome are linked with mental illnesses such as anxiety and depression. Interestingly, it is the overall ratio of different species rather than individual species that appear to be responsible for this effect. Hence, gut bacteria appear crucial in maintaining our wellbeing. (43)

A Word from Mindset Health:

The gut-brain axis joins the digestive system and nervous system and plays an important role in overall health. The brain-gut connection is made up of 'the second brain' - nerve cells of the enteric nervous system - the vagus nerve and gut microbiota. These features are influenced directly by the stress response, which may lead to health problems of the digestive tract such as irritable bowel syndrome (IBS). By contrast, maintaining a healthy gut by consuming foods beneficial to the gut microbiome can improve symptoms of IBS and protect against brain diseases such as Alzheimer's and Parkinson's disease. The gut-brain connection is therefore critical to the health of the gastrointestinal tract and the good health of the mind.

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Our Sources

Mindset Health only uses high-quality sources, including peer-reviewed research, to support our articles. We work with experts to ensure our content is helpful, accurate and trustworthy.

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