August 7, 2019

Anxiety & the Gut: Are they linked & what is the link?

by Dr. Miles Nichols and Nicola Schuler, CNTP, MNT

A tremendous amount of recent research has established a link between the gut and the brain. There is a gut-brain axis, which regulates brain function and behavior (Chunlong Mu, 2016).

The gut-brain axis plays a critical role in neuropsychiatric disorders like anxiety, depression, schizophrenia, dementia and autism (Kim YK, 2018).

Anxiety has been shown to be deeply affected by the gut–brain axis. In this article, we will explore this connection in more detail and suggest ways to address anxiety using the latest research on the gut-brain link.

  • Anxiety disorders are the most common mental illness in the U.S., affecting 40 million adults in the United States age 18 + (1% of the population) every year (Anxiety and Depression Association of America Facts & Statistics).
  • Approximately one in four adults in the US will suffer from an anxiety disorder at some point in their lives. (Murrough JW, 2015)
  • Worldwide, 4 out of every 100 people suffer from an anxiety disorder, but North America appears to have a higher than average rate (8 in 100), while East Asia had the lowest rate (3 in 100). (Mulpeter, 2017)
  • Patients with anxiety disorders experience substantial physical and emotional discomfort and have elevated rates of substance use and medical illnesses. (Murrough JW, 2015)
  • Anxiety disorders are more common among women, who were nearly twice as likely to be affected as men. Other at-risk groups include adults under age 35, and people with chronic diseases such as cardiovascular disease, COPD, diabetes, and cancer. (Mulpeter, 2017)

Anxiety can be mild to debilitating. The main feature of anxiety disorders is excessive fear and anxiety and behavioral disturbances that occur as a result. Common anxiety signs and symptoms include (Mayo Clinic, Anxiety disorders):

  • Feeling nervous, restless or tense
  • Having a sense of impending danger, panic or doom
  • Having an increased heart rate
  • Breathing rapidly (hyperventilation)
  • Sweating
  • Trembling
  • Feeling weak or tired
  • Trouble concentrating or thinking about anything other than the present worry
  • Having trouble sleeping
  • Experiencing gastrointestinal (GI) problems
  • Having difficulty controlling worry
  • Having the urge to avoid things that trigger anxiety

How does the gut brain axis work in relation to anxiety?

The gut brain axis refers to biochemical signaling between the gut and the brain. Broadly defined, the gut–brain axis includes the nervous system, the immune system and the endocrine (or hormone) system.

The ‘microbiome–gut–brain axis’ explicitly includes the role of gut flora in the biochemical signaling events that take place between the GI tract and the brain. This is important because gut microbiota, i.e. bacteria in the gut, regulate neurophysiological behaviors through neural, endocrine and immune pathways (Collins, 2012).

  • Vagus nerve: Neurons are nerve cells which transmit nerve impulses and communicate with each other. Neurons are in the brain and the gut and they communicate with each other via the vagus nerve. The vagus nerve is a large nerve connecting the brain and the gut, sending signals in both directions, and is involved in control of mood, immune response, digestion, and heart rate (Breit S, 2018).  Breathing, meditation and yoga stimulate the vagus nerve and decrease mood and anxiety symptoms (Breit S, 2018).
  • HPA axis: The gut brain axis includes the HPA axis. The HPA axis is part of the endocrine (hormone) system and regulates stress and the stress hormones. Stress, especially chronic stress, affects and changes the microbiome (Liu L, 2018). Stress activates the HPA axis and increases cortisol (a stress hormone) levels leading to increases in anxiety levels and intestinal microbiota changes (Liu L, 2018). Thus the change in the microbiome affects mood. Conversely, the intestinal microbiota can also inhibit the increase of cortisol through the HPA axis to relieve anxiety and depression (Liu L, 2018). Therefore, the HPA axis plays a bi-directional role in the gut-brain axis.
  • Neurotransmitters or NT’s: Neurotransmitters are chemical messengers produced in the brain. They transmit signals from one neuron to another neuron, muscle cell, or gland cell. They control feelings and emotions. The neurotransmitter serotonin contributes to feelings of happiness (Anguelova M, 2003). Gamma-aminobutyric acid, or GABA, is another NT which helps control feelings of fear and anxiety (Mazzoli R, 2016). Neurotransmitters are also produced by gut cells and the trillions of microbes living there. For example, a large proportion of serotonin is produced in the gut (Anguelova M, 2003).
  • Short-chain fatty acids or SCFAs: The trillions of microbes that live in the gut also make other chemicals that affect how the brain works (Clarke G, 2014). Gut microbes produce short-chain fatty acids such as butyrate, propionate and acetate. They are related to regulating the immune system and their absence or reduced status in the gut can contribute to inflammation in the gut (Hirschberg S, 2019). In a study on anxiety, low levels of SCFA-producing bacteria were found in patients with anxiety as compared to healthy controls without anxiety (Jiang HY, 2018).
  • Immune system: The gut plays an important role in immunity. 70-80% of immune cells are located in the gut. Gut bacteria provides crucial signals for immune system function. The gut controls what enters the body and what does not. If there is intestinal permeability, or leaky gut, inflammation occurs. The immune system will over-react and this can lead to disorders associated with inflammation like depression, Alzheimer’s and autoimmunity. Chronic low-grade inflammation causes cytokines, inflammatory molecules, to be released into the blood, further affecting the immune system. Intestinal microbiota contain molecules that can cause inflammation. The indirect effects of intestinal microorganisms on the immune system can cause changes in the circulating levels of pro-inflammatory and anti-inflammatory cytokines, which in turn have direct impacts on brain function (Kim YK, 2018).

Anxiety & the Gut

Anxiety is a multi-factorial disorder prompted by certain environmental factors in genetically susceptible individuals (Cenit MC, 2017). There is an element of complex gene-environment interactions and gut microbiota changes that precede the onset of neuropsychiatric diseases such as anxiety (Cenit MC, 2017).

Risk factors include genetics, brain chemistry, personality, and life events. (Anxiety and Depression Association of America Facts & Statistics). Anxiety can be triggered by a difficult or traumatic event (i.e. an accident, divorce, death of a loved one), trauma, chronic stress and in many other situations.

While genetics play a role in the possibility of developing anxiety, there are people with the same genetics who develop anxiety and others who never experience anxiety as an issue. In this article we will focus on modifiable risk factors that you can take some action towards changing.

There is a clear link between the gut brain axis and anxiety. About 60% of anxiety and depression patients have disturbed gastrointestinal function, such as in irritable bowel syndrome (IBS) (Liu L, 2018).

Treatment to date for anxiety is often therapy, typically in conjunction with anti-anxiety or anti-depression medications such as SSRIs (selective serotonin reuptake inhibitors). In the case of generalized anxiety, treatment response rates for SSRIs of between 60 and 75% are generally reported in studies, compared to response rates of between 40–60% for placebo (Lach G, 2018). While these rates are not insignificant, the issue with using SSRIs is that they do not address the root causes of the anxiety.

It is more effective to identify and address the root cause or causes of anxiety and avoid taking medication for the rest of your life. Furthermore, these drugs can have unintentional side effects. Antidepressants are well known to have antimicrobial effects and can damage the health of the gut microbiome (Lach G, 2018). This will reshape not only brain biochemistry, but also the gut microbiota, and not for the better (Lach G, 2018). The negative implications of antidepressants on gut health may result in intensifying anxiety over the long term, in a vicious cycle.

Furthermore, anxiety has various causes. If the root cause or causes are not addressed, treatment success rates over time are low (Kim YK, 2018). Emerging evidence of the interactions among the brain, gut, and microbiome can help those suffering from anxiety and the mechanisms underlying these complex interactions (Kim YK, 2018).

Gut health is critically important in cases of anxiety.  Before we address specific solutions to anxiety, let’s take a look at what can negatively impact the health of the gut microbiome (Mu C, 2016):

  • Diet
    • Sugar & excess refined carbohydrates
    • GMOs
    • Highly processed foods
    • Lack of fiber
    • Excess caffeine
    • Excess alcohol
  • Genetic make-up of the individual
  • Inflammation, particularly if in the gut
  • GI issues like dysbiosis (an unbalanced gut flora), leaky gut and many others
  • Antibiotics, SSRIs for depression or anxiety, NSAIDs and other medications
  • Circadian rhythm dysregulation
  • Stress – physical or emotional
  • Environmental toxins – mold, chemicals & others
  • Habits – news/ media, electronic use, lack of sleep, addictions, etc.
  • Abusive relationships, excessively stressful job, and history of trauma that has not been adequately processed/ resolved

Solutions:  What can you do?

Fix your gut: Like many other conditions we have written about in our blog, it is necessary to work on gut healing when addressing anxiety.

Inflammation in the gut is a key factor in neuropsychiatric conditions like anxiety. We’ve mentioned leaky gut but there can be other sources of gut inflammation.

Dysbiosis (an imbalance of good and bad bacteria in the gut), bacterial overgrowth like SIBO (small intestinal bacterial overgrowth), yeast overgrowth like Candida, a shortage of SCFAs, histamine intolerance, parasites, IBS, and other gut issues can all cause gut inflammation.

We recommend working with a functional medicine practitioner to identify any GI issues, infections or overgrowths when addressing anxiety.

Additionally, it can be helpful to work with an expert on issues like rebalancing neurotransmitter levels, increasing SCFAs in your gut, stimulating vagus nerve function, rebalancing an imbalanced HPA axis or stress response, and ensuring that your overall gut function is optimal.

Diet: Certain foods are particularly helpful for the gut-brain axis.

Some of the most important ones are:

  • Omega-3 fats: These are good fats found in wild salmon, sardines, anchovies, mackerel and herring as well as in high quantities in the brain. Studies in humans and animals show that Omega-3 fats can increase good bacteria in the gut and reduce risk of brain disorders (Robertson RC, 2017), (RJT Mocking, 2016).
  • Probiotic-rich fermented foods: Yogurt, kefir, sauerkraut, natto, kimchi and kvass all contain healthy microbes that are beneficial to gut health.  One study found that fermentation enhances the specific nutrient and phytochemical content of foods, which is associated with mental health (Selhub EM, 2014). In addition, the microbes (Lactobacillus and Bifidobacteria species) associated with fermented foods may also influence brain health via direct and indirect pathways (Selhub EM, 2014).
  • Prebiotic foods:  Prebiotics have been reported to improve inflammation and to alleviate psychological distress (Kim YK, 2018).  These foods contain non-digestible fibers that promote the growth of beneficial gut microbiota such as Lactobacillus and Bifidobacterium, benefiting the microbial-gut-brain axis (Kim YK, 2018). Prebiotic foods include lentils, apple cider vinegar, dandelion greens, raw garlic, raw or very lightly cooked onion, leeks, raw asparagus, green bananas, green plantains, potatoes that have been cooked then cooled 24 hours (served cold or at room temperature, as is common in potato salad), apples and others.
  • Polyphenol-rich foods: Clove, berries, raw cocoa, green tea, olive oil and coffee all contain polyphenols, which are plant chemicals that are digested by gut bacteria. Polyphenols increase healthy bacteria in the gut and can improve neuro-inflammation, inflammation in the brain, commonly found with depression and anxiety (Matarazzo I, 2018). These foods have been reported to promote cognitive function (Filosa S, 2018). One of our favorite polyphenol-rich foods we recommend to patients is pomegranate juice. While we normally don’t recommend fruit juices due to sugar content, research on pomegranate has shown such a high concentration of polyphenols that it tends to favorably impact blood sugar, likely due to its beneficial effects on the gut (here’s a link to an article we did on pomegranate).
  • Tryptophan-rich foods: Tryptophan is an amino acid that is converted into the neurotransmitter serotonin. Serotonin regulates mood, anxiety, stress, aggression, feeding, cognition and sexual behavior (Olivier B, 2015). Low serotonin is thought to be associated with anxiety (Olivier B, 2015). By increasing tryptophan through diet, the gut is better nourished to make serotonin. Foods that are high in tryptophan include turkey, eggs and cheese.

 Probiotics

Probiotics are live microorganisms that stimulate the growth of gut bacteria and enhance gut health.  Studies on probiotics have shown that low-grade inflammation is reduced, gut permeability is restored, and the composition of the gut microbiome changes (Kim YK, 2018). Probiotics modulate the processing of information that is strongly linked to anxiety and depression and influence the stress response. (K Schmidt, 2014).

Multiple studies have looked at specific strains of probiotics and found the following:

  • Lactobacillus casei Shirota – Improved mood in those who initially had poor mood, Better long-term memory (Kim YK, 2018)
  • L. helveticus, B. longum – Improvement of anxiety and depression symptoms (Kim YK, 2018)
  • L. acidophilus, L. casei, L. rhamnosus, L. bulgaricus, B. lactis, B. breve, B. longum, S. thermophiles – Improvement of anxiety and depression symptoms (Kim YK, 2018)
  • B. bifidum, B. lactis, L. acidophilus, L. brevis, L. casei,  L. salivarius, Lactococcus lactis – Improvement of self-reported mood and sadness (Kim YK, 2018)
  • L. casei Shirota – Decreased anxiety symptoms (Kim YK, 2018)
  • Lactobacillus rhamnosus – Reduced stress-induced anxiety- and depression-like behaviors in mice, Decreased levels of stress-induced hormones and changed levels of the NT GABA throughout the brain (Sharon G, 2016)
  • Lactobacillus rhamnosus and Lactobacillus helveticus – Reduced anxiety-like behaviors in mice in another study (Sharon G, 2016)
  • Bacteroides fragilis – Corrected anxiety-like and repetitive behaviors in mice, Partially restored an impaired microbiome, Restored intestinal barrier function (Sharon G, 2016)

Prebiotics

  • Prebiotics increase the level of Bifidobacterium, a healthy gut bacteria in the intestinal tract, benefitting the microbial-gut-brain axis (Kim YK, 2018)
  • The effect of prebiotics and increased Bifidobacterium can increase levels of Lactobacillus, Bacteroide and Bifidobacterium, other probiotic strains, in the gut (Kim YK, 2018)
  • Prebiotics increase the production of SCFAs as a result of the healthier gut flora profile (Kim YK, 2018)
  • In both animal and human studies, prebiotics have improved inflammation and reduced psychological distress (Kim YK, 2018)
  • One study showed prebiotics reduced stress and its effects, which positively impacts the microbiome (Kim YK, 2018)

Fecal Microbiota Transplantation (FMT)

FMT is the transplant of healthy human feces to a patient with severe gut dysbiosis, in order to regulate the intestinal microbiota of the patient. When the normal gut microbiota are destroyed, for example by excessive antibiotic treatment or other negative substances like GMO foods, it can be challenging to recover a normal healthy bacterial flora. FMT can be extremely helpful in these situations (Kim YK, 2018).

FMT can be an effective treatment for IBS. IBS showed a remission rate of 36-89% after FMT treatment (Kim YK, 2018). Recently, the first FMT trial in a neuropsychiatric area took place. In this eight-week clinical trial to evaluate the impact of FMT on GI and psychiatric symptoms, both GI and psychiatric symptoms were significantly reduced and Improvements were measured to have lasted eight weeks after treatment (Kim YK, 2018).

Many factors can affect anxiety and mood. Some may be a relatively simple and quick fix that you can do on your own like diet changes, while others may be more complex like FMT. Some other approaches to consider with anxiety include:

  • Balance blood sugar – Living on the blood sugar rollercoaster with excessive swings in blood sugar create and/or worsen mood issues like anxiety and depression.
  • Reduce caffeine consumption – Caffeine is a stimulant and can make you feel on edge or anxious. This is especially true for people who are slow metabolizers of caffeine.
  • Identify food sensitivities and allergies and eliminate those foods – Common allergenic foods like gluten, dairy, soy and corn can contribute to symptoms.
  • Address a potential magnesium deficiency – Research has shown that magnesium can help decrease anxiety in magnesium–deficient people (Boyle NB, 2017).
  • Reduce, where possible, and manage stress levels
  • Practice mindfulness and meditate daily
  • Work with an expert to process any past traumas
  • Deep diaphragmatic breathing – Breathing exercises can help to stimulate the vagus nerve and slow both heart rate and blood pressure.

If you or someone you know is suffering from anxiety, get in touch with our clinic today. Book a free 15-min discovery call to see how we can help you with your symptoms. We can answer your questions and help you book an initial consult with one of the functional medicine doctors in our clinic.

References:

Anguelova M, B. C. (2003). A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: I. Affective disorders. Mol Psychiatry.

Anxiety and Depression Association of America Facts & Statistics. (n.d.). Retrieved July 9, 2019, from Facts & Statistics: https://adaa.org/about-adaa/press-room/facts-statistics

Boyle NB, L. C. (2017). The Effects of Magnesium Supplementation on Subjective Anxiety and Stress-A Systematic Review. Nutrients.

Breit S, K. A. (2018). Vagus Nerve as Modulator of the Brain-Gut Axis in Psychiatric and Inflammatory Disorders. Front Psychiatry.

Cenit MC, S. Y.-F. (2017). Influence of gut microbiota on neuropsychiatric disorders. World J Gastroenterol.

Chunlong Mu, Y. Y. (2016). Gut Microbiota: The Brain Peacekeeper. Frontiers in Microbiology.

Clarke G, S. R. (2014). Minireview: Gut Microbiota: The Neglected Endocrine Organ. Mol Endocrinol.

Collins, S. M. (2012). The interplay between the intestinal microbiota and the brain. Nat. Rev. Microbiol. 10.

Filosa S, D. M. (2018). Polyphenols-gut microbiota interplay and brain neuromodulation. Neural Regen Res.

Hirschberg S, G. B. (2019). Implications of Diet and The Gut Microbiome in Neuroinflammatory and Neurodegenerative Diseases. Int J Mol Sci.

Jiang HY, Z. X. (2018). Altered gut microbiota profile in patients with generalized anxiety disorder. J Psychiatr Res. .

K Schmidt, P. C. (2014). Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers. Psychopharmacology (Berl).

Kim YK, S. C. (2018). The Microbiota-Gut-Brain Axis in Neuropsychiatric Disorders: Patho-physiological Mechanisms and Novel Treatments. Current Neuropharmacology.

Lach G, S. H. (2018). Anxiety, Depression, and the Microbiome: A Role for Gut Peptides. Neurotherapeutics.

Liu L, Z. G. (2018). Gut–Brain Axis and Mood Disorder. Front Psychiatry.

Matarazzo I, T. E. (2018). Psychobiome Feeding Mind: Polyphenolics in Depression and Anxiety. Curr Top Med Chem.

Mayo Clinic, Anxiety disorders. (n.d.). Retrieved July 9, 2019, from Mayo Clinic: https://www.mayoclinic.org/diseases-conditions/anxiety/symptoms-causes/syc-20350961

Mazzoli R, P. E. (2016). The Neuro-endocrinological Role of Microbial Glutamate and GABA Signaling. Front Microbiol.

Mu C, Y. Y. (2016). Gut Microbiota: The Brain Peacekeeper. Front. Microbiol.

Mulpeter, K. (2017, January 31). These Groups Are Most at Risk for Anxiety Disorders. Retrieved July 9, 2019, from Health: https://www.health.com/anxiety/anxiety-disorders-women

Murrough JW, Y. S. (2015). Emerging Drugs for the Treatment of Anxiety. Expert Opin Emerg Drugs.

Olivier B, O. (2015). Serotonin: a never-ending story. Eur J Pharmacol.

RJT Mocking, I. H. (2016). Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder. Transl Psychiatry.

Robertson RC, S. O. (2017). Omega-3 polyunsaturated fatty acids critically regulate behaviour and gut microbiota development in adolescence and adulthood. Brain Behav Immun. .

Selhub EM, L. A. (2014). Fermented foods, microbiota, and mental health: ancient practice meets nutritional psychiatry. J Physiol Anthropol.

Sharon G, S. T. (2016). The Central Nervous System and the Gut Microbiome. Cell.

 

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Michelle Davis - October 30, 2019 Reply

Thank You for the very educational e-mails. I found this one especially helpful in my understanding of how important it is to do our part when it comes to what we put in our stomachs. Hope all is going well with you and that you are able to help lots of folks. God Bless Michelle Davis

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