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Depression is a mental disorder and the leading cause of disability, reaching the whole world (Ferrari et al., 2013) and being the most debilitating and recurrent stress-related disorder that highly impact the quality of life of people affected (Moussavi et al., 2007). The estimated prevalence of major depressive disorder (MDD) reaches the 4.4% of the world population, equivalent to 322 million people living with depression (World Health Organization, 2017).

The symptoms include, depressed mood, anhedonia (inability to feel pleasure), irritability, difficulty concentrating, changes in appetite and sleep (Nestler et al., 2002) and is also associated with psychological and functional impairment, cognitive deficits, increased risk of suicidal behaviour, and increased mortality (Amidfar, Réus, Quevedo, & Kim, 2018).  

depressionThe most used theory to explain depressive symptoms points to decreased levels of neurotransmitters (serotonin, noradrenalin and dopamine) in synaptic clefts (gaps), which are the spaces between two neurons across which nerve impulses are passed.  Today, these effects are treated pharmacologically by antidepressants. Nevertheless, recent evidence has shown that depressed patients have altered gut microbiota (Jiang et al., 2015; Kelly et al., 2016; Zheng et al., 2016), so new pathways are being investigated to understand better the physiology of depression.

One of them is studying the gut microbiota, and their communication with the brain via the gut-brain axis.  This pathway is important, complex, and bidirectional (Rhee, Pothoulakis, & Mayer, 2009).  The brain influences the gastrointestinal tract, and the gut influences brain functions, especially those involved in stress (Hannan, 2016). Dysregulation of this communication is evident in patients with depression. All these findings suggest that nowadays, depression should not be conceived only as a mental disorder of the brain, but as a more systemic disorder also involving the gut.

Following this line of research, gut microbiota should be investigated and discussed as an important neuropharmacological target for depression. A 2001 study confirmed the role of inflammation in depressive disorders (Reichenberg et al., 2001).  More recent investigations indicate that changes in the gut microbiota (due to illness, stress, change in nutrition) can lead to a systemic inflammation that reaches the central nervous system (CNS).

Clinical studies have been carried out with probiotics, living microorganisms that inhabit the intestines that contribute to human health. These investigations have supported that probiotic bacteria have positive effects on the central nervous system and suggest that dosing might improve mental function in patients with depression and other mental disorders (Ansari, Pourjafar, Tabrizi & Homayouni, 2020).  Thus, modulating the composition of the microbioma can effect the brain and behaviour via gut-brain axis communication pathway (Parashar et al.,2019 and Felice et al., 2017).  Other studies also show that probiotic treatment markedly reduces depressive-like behaviour (Abildgaard et al., 2017)  and that probiotics taken by patients have resulted in antidepressant responses (Carlessi et al., 2019). 

These findings help elucidate the pathophysiology of depression and to show the need to study new therapeutic strategies to improve its treatment. In line with this and looking toward the future, the evidence accumulated deserves increasing attention in the biological psychiatry of depression (Bastiaanssen et al., 2020) and new treatments for depression will consider the microbioma.

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References

Abildgaard, A., Elfving, B., Hokland M., Wegener, G., and Lund, S. (2017). Probiotic treatment reduces depressive-like behaviour in rats independently of diet. Psychoneuroendocrinology 79, 40–8. doi:10.1016/ j.psyneuen.2017.02.014.

Amidfar, M., Réus, G. Z., Quevedo, J., & Kim, Y. K. (2018). The role of memantine in the treatment of major depressive disorder: Clinical efficacy and mechanisms of action. European Journal of Pharmacology, 827, 103–111. https ://doi.org/10.1016/j.ejphar.2018.03.023.

Ansari, F., Pourjafar, H., Tabrizi, A., and Homayouni, A. (2020). The Effects of of Probiotics and Prebiotics on Mental Disorders: a Review on Depression, Anxiety, Alzheimer, and Autism Spectrum Disorders. Current Pharmaceutical Biotechnology, doi: 10.2174/1389201021666200107113812.

Bastiaanssen, T., Cussotto, S., Claeson, M.,Clarke, G., Dinan, T. and Cryan, J. (2020) Gutted! Unraveling the Role of the Microbiome in Major Depressive Disorder.  Harvard Review of Psichiatry, 28(1), 26-39.

Carlessi, A., Borba, L., Zugno, A., Quevedo, J., Réus, G. Gut-microbiota-brain axis in depression: the role of neuroinflammation [published online November 30, 2019]. Eur J Neurosci. doi: 10.1111/ejn.14631.

Felice V, et al. (2017). Pharmacol, Biochem Behav,160,1-13.

Ferrari, A. , Charlson, F. , Norman, R., Patten, S., Freedman, G., Murray, C. J., … Whiteford, H. (2013). Burden of depressive disorders by country, sex, age, and year: Findings from the global burden of disease study 2010. PLoS Medicine, 10, e1001547. https ://doi.org/10.1371/journ al.pmed.1001547.

Hannan, A. J. (2016). Thinking with your stomach? Gut feelings on mi-crobiome modulation of brain structure and function (Commentary on Luczynski et al.). European Journal of Neuroscience, 44, 2652–2653. https ://doi.org/10.1111/ejn.13399.

Jiang, H., Ling, Z., Zhang, Y., Mao, H., Ma, Z., Yin, Y., … Ruan, B. (2015). Altered fecal microbiota composition in patients with major depressive disorder. Brain, Behavior, and Immunity, 48, 186–194.
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Moussavi, S., Chatterji, S., Verdes, E., et al. (2007) Depression, Chronic Diseases, and Decrements in Health: Results from the World Health Surveys. The Lancet, 370, 851-858.
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Rhee, S. H., Pothoulakis, C., & Mayer, E. A. (2009). Principles and clinical implications of the brain-gut-enteric microbiota axis. Nature Reviews Gastroenterology & Hepatology, 6, 306–314. https ://doi.org/10.1038/nrgas tro.2009.35

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Zheng, P., Zeng, B., Zhou, C., Liu, M., Fang, Z., Xu, X., … Xie, P. (2016). Gut microbiome remodeling induces depressive-like be-haviors through a pathway mediated by the host’s metabolism. Molecular Psychiatry, 21, 786–796.

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About the author

Carolina Ramos is a research associate in the Project eat2beNICE at the Group of Psychiatry, Mental Health and Addictions, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain. She has a degree in Chemistry and Psychology from the Universitat Autònoma de Barcelona and from the Universitat Oberta de Catalunya respectively. Carolina has developed her professional activity as project manager of research projects in diferent areas and also conducting studies in neurodeveloptment disorders, especially in ADHD .


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