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“A healthy mind in a healthy body” is a translated Latin phrase by Roman poet, Juvenal, and is widely referenced in sporting and educational contexts to describe the association between healthy eating and exercise as an important part of mental and psychological wellbeing.

On this note, emerging evidence over the past decade has suggested that a healthy gut microbiome is a novel therapeutic target for the treatment and/or prevention of mood and anxiety disorders, and subsequently, a healthy mind.1

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The Gut Talks

There is a recent field of research which highlights that direct biochemical signalling exists between the gastrointestinal tract and the central nervous system, which is named the ‘gut–brain axis’.1,2

The gastrointestinal tract is connected to the brain via 200 to 600 million neurons3 and this microbiome–gut–brain axis is said to be essential for maintaining homeostasis, including that of the central nervous system.4 Furthermore, modulation of this gut–brain axis is linked to behaviour and the stress response.4,5

The human microbiome is under constant dynamic evolution throughout the host’s lifetime, and populations exist on numerous sites of the body (e.g. skin, oral cavity, the vagina and the gastrointestinal tract).4

To get a picture of how large the adult microbiome actually is in relation to the gut, consider that there are approximately 1014 microorganisms residing inside the gastrointestinal tract (which is roughly 10x the amount of human cells in the body).4

The majority of said 1014 microorganisms are bacterial, comprised of around 500 to 1000 different species which can vary in number, diversity and stability across the human population.4

This microbiome is also sensitive to a wide range of influences such as infection, diet, stress and pharmacological intervention.4

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Mood Disorders and the Gut

Major depressive disorder is a complex psychiatric condition that will affect up to 20% of the population at some point in their life, with most pharmacological treatments focusing on altering neurotransmitter activity in the brain.2

These conventional treatments (i.e. antidepressants) can cause adverse effects such as nausea, sedation, headaches and sexual dysfunction.2

The link between depression and probiotics is suggested by Logan and Katzman6 who state that the beneficial bacteria which are lowered in states of stress and illness could influence depression by a number of mechanisms.

This is evidenced by the Tannock and Savage7 study, which found that stressed mice had lower levels of lactobacilli compared with control mice.

Further to this point, Liu et al.8 note that stress is considered to be correlated to anxiety and depression.

Additionally, recent study findings suggest that stress leads to anxiety and depression by altering the gut microbiota.8

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Are Probiotics the Solution?

There is consequently a growing body of evidence that probiotics can be utilised to normalise the microbial imbalance associated with psychological conditions.9

Probiotics are defined as: live microorganisms that improve the host intestinal microbial balance when administered in adequate amounts.6,10

In studies, probiotics have been found to decrease oxidative stress and lower systemic inflammatory cytokines6, both of which have been associated with mood disorders.11

Furthermore, there is robust evidence in animal studies that have found improvements in mood, anxiety and cognition by altering neurotransmitter activity through the administration of probiotics.2

Other animal studies have observed changes in the metabolism and biosynthesis of the imperative neurotransmitter, serotonin.2

Additionally, preclinical studies have found that psychological changes such as reduced anxiety and depressive-like behaviours were observed in rodents that were treated with probiotics.12

Conversely, in regards to human trials, the recent double-blind, randomised, placebo-controlled trail by Romijn et al.11, found no significant difference between probiotic and placebo groups across any of the psychological outcome measures.

Despite this, however, the authors noted several distinct limitations to their study (e.g. treatment-resistant sample) and strongly encouraged future studies in this area.11

Furthermore, a 2017 systematic review of several trials involving humans found that the majority of studies had positive results on all measures of depressive symptoms.2

Of note though, the dosing, duration of treatment and strain of probiotic varied significantly between studies.2

Researchers have thus queried that the beneficial effects of probiotics on depression and anxiety may be strain specific.1

Nonetheless, the research in this area indicates that probiotics may improve symptoms associated with major depressive disorders by decreasing levels of anti-inflammatory markers and/or increasing serotonin.2

Such a novel treatment option in this space has the potential to reduce the latency, stigma and side effects associated with conventional antidepressants.2

Studies have also suggested that human microbiota could be a target for the prevention of anxiety and depression in at-risk populations, given the role that microbiota plays in neurodevelopment of brain networks related to emotion regulation.1

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Future Implications

In summary, it is clear from the convincing evidence in preclinical studies that further research is warranted to determine the efficacy of probiotics in treating depressive symptoms and anxiety.

The ideal strain of probiotic still requires clarification, as well as the treatment duration and dose to provide the best outcomes in humans.

Who knows, a healthy gut may really be the answer to a healthy mind.


Written by Kate Ellis
B.Pharm Cert IV TAE, Professional Practice Pharmacist, National Guild Intern Training Program, The Pharmacy Guild of Australia, Queensland Branch


References

1. Slyepchenko A, Carvalho A, Cha D, Kasper S, McIntyre R. Gut Emotions – Mechanisms of action of probiotics as novel therapeutic targets for depression and anxiety disorders. CNS Neurol Disorder Drug Targets. 2014, 13(10):1770–86.
2. Wallace C, Milev R. The effects of probiotics on depressive symptoms in humans: a systematic review. Ann Gen Psychiatry. 2017, 16(14):1–10.
3. Furness J. Novel gut afferents: intrinsic afferent neurons and intestinofugal neurons. Auton Neurosci. 2006, 125:81−85.
4. Moloney R, Desbonnet L, Clarke G, Dinan T, Cryan J. The microbiome: stress, health and disease. Mamm Genome. 2014, 25:49–74.
5. Clarke G et al. The microbiome–gut–brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Mol Psychiatry. 2013, 18(6):666–73.
6. Logan A, Katzman M. Major depressive disorder: probiotics may be an adjuvant therapy. Med Hypotheses. 2005, 64(3):533–8.
7. Tannock G, Savage D. Influences of dietary and environmental stress on microbial populations in the murine gastrointestinal tract. Infect Immun. 1974, 9:591−98.
8. Liu X, Cao S, Zhang X. Modulation of gut microbiota-brain axis by probiotics, prebiotics, and diet. J Agric Food Chem. 2015, 63(36):7885–95.
9. Saulnier D, Ringel Y, Heyman M. The intestinal microbiome, probiotics and prebiotics in neurogastroenterology. Gut Microbes. 2013, 4(1):17−27.
10. Hill C, Guarner F, Reid G et al. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. 2014, 11:506−14.
11. Romijn A, Rucklidge J, Kuijer R, Frampton C. A double-blind, randomized, placebo controlled trial of Lactobacillus helveticus and Bifidobacterium longum for the symptoms of depression. Aust N Z J Psychiatry. 2017, 1–12.
12. Luo J, Wang T, Liang S, et al. Ingestion of Lactobacillus strain reduces anxiety and improves cognitive function in the hyperammonemia rat. Sci China Life Sci. 2014, 57(3):327–35.