Depression is a major concern, as it greatly adds to the burden of disease on a global scale. According to World Health Organization (2018), there are more than 300 million depressed individuals of all ages and the numbers are expected to increase. Thus, effective treatment methods for major depressive disorder should be a priority.
There is a variety of treatments currently available, with antidepressants being most commonly used, as they target the emotional neural system. While they are effective in most cases, they also produce pharmacotherapeutic side effects (Balikci et al, 2014). Cognitive Behavioral Therapy is another frequently used method, which is primarily focused on psychological interventions. However, it is expensive and time-consuming (Lepping et al, 2017). With that being said, alternatives for major depressive disorder are needed.
Psychobiotics has been placed as a subject of interest and extensively explored by scientists and researchers over the past couple of years. Our gut microbiota hosts a commensal relationship of beneficial bacteria known as probiotics, which are stimulated by growth promoting non-digestible food components called prebiotics. These microbiome constituents are termed psychobiotics. They induce a bacterially-mediated impact on the brain, which consequently influences the immune and nervous systems of the body (Sarkar et al, 2016).
Psychobiotics are probiotics, or live bacteria, that produce beneficial mental effects when ingested in adequate amounts. These live microorganisms are typically found in the gut.
Interestingly, the human gut is connected to the brain through the gut-brain axis, a bidirectional communication system, which is mediated by both neural and humoral mechanisms. There are various neural pathways in this particular axis, including autonomic and enteric pathways, and hypothalamic-pituitary-adrenal (HPA) axis. The slow humoral route combined with the rapid neural pathways facilitates gut microbiota’s effects on brain and behavior (Bruce-Keller, Salbaum, & Berthoud, 2018). This allows the microbiota to have a significant effect on the symptoms of mental disorders.
Psychobiotics could treat a variety of mental disorders effectively, which include disorders of mood, behavior, and cognition. In fact, psychobiotics “exert anxiolytic and antidepressant effects characterized by changes in emotional, cognitive, systemic, and neural indices” (Sarkar et al, 2016).
More importantly, psychobiotics can help alleviate the symptoms of depression since they can reduce inflammation, its microbial composition has a relationship with mental disorders, and can relieve anxiety-like behavior.
Reduction of Inflammation
Psychobiotics can alleviate symptoms of depression, particularly by reducing inflammation. Cytokines are a type of proteins secreted by immune cells, which act as chemical messengers, that play a major role in regulating inflammatory responses. Pro-inflammatory cytokines, cytokines that promotes inflammatory responses, are found to be very elevated in the blood of individuals with depressive behavior and other inflammatory and mood disorders (Park et al, 2018).
Interestingly, psychobiotics can decrease pro-inflammatory cytokines and increase anti-inflammatory cytokines. A study was conducted on Sprague–Dawley rats to test the effects of microbiota on inflammation. A stress factor was introduced to their physiology. Due to their evident anxious and depressive symptoms that were accompanied with reduced levels of noradrenaline, elevated inflammation and stress markers such as corticotropin-releasing hormone, a group of rats were injected with antidepressants and others with the microbiota Bifidobacterium infantis.
Inflammation and Depression
Ultimately, the introduction of a probiotic has regularized the altered psychophysiological state resulting in an analogous effect to that exerted by antidepressants (Sarkar et al, 2016). Thus, by normalizing the gut microbiota composition and reducing the inflammation, psychobiotics alleviate the symptoms of depression.
Gut Microbial Composition
The importance of gut microbial composition is evident, as the diversity of gut microbiota varies from healthy individuals to patients diagnosed with major depressive disorder. The human gut serves as a natural habitat for the complex microbiome population. When an individual reaches adulthood, a relative equilibrium of bacterial abundance and diversity is reached in the microbiome.
Typically, the abundance and diversity remain unchanged under stable health or environmental conditions. However, the microbiome could be affected by several factors such as disease, infection, and diet (Dinan, Stanton, & Cryan, 2013), which in turn, disrupt its composition.
Microbial Diversity and Depression
Evidence suggests that microbial diversity may play a role in the risk of depression. For instance, a study has shown that there’s a significant difference in the beta-diversity between the gut microbiota of major depressive disorder and the gut microbiota of healthy individuals (Zheng et al, 2016).
The fact that there is less bacterial richness and diversity in the microbial populations of depressed individuals indicates that an abnormal microbial composition may be involved the development of major depressive disorder.
Additionally, psychobiotics can decrease the risk of depression, as studies have shown that these live microorganisms can help restore the microbial composition and maintain a healthy community of microbiota (Park et al, 2018).
Results show that gut microbiota may be highly correlated to the process that underlies the development of depression, as the alteration in the microbial composition was enough to disrupt behavioral and physiological homeostasis in rats that lacked microbiota.
Regulation of HPA Stress Response
Psychobiotics can also help treat symptoms of depression by reducing stress through the regulation of HPA stress response and by synthesizing neurotransmitters that are typically deficient in individuals suffering from depression.
Elevated cortisol levels may serve as a trait marker for the susceptibility of depression, as a dysregulation of the HPA axis has often been found in individuals diagnosed with depression (Ancelin et al, 2017). The gut-brain axis, a network of bidirectional communication between the brain and gut, allows microbiota to have significant effects on the symptoms of neurodevelopmental disorders, such as major depressive disorder.
The dysregulation of microbiota-gut-brain axis leads to the stress response, particularly cortisol, which is produced by a complex interaction among the hypothalamus, the pituitary gland, and adrenal glands. The hypothalamic-pituitary-adrenal (HPA) axis is a neural pathway in the gut-brain axis, which happens to be a major output of cortisol.
Essentially, when the brain detects a threat, it signals the hypothalamus to produce a hormone, which stimulates the pituitary gland to produce another hormone that causes the adrenal gland to release cortisol (Burokas, Moloney, Dinan, & Cryan, 2015).
HPA and Depression
The microbiota-gut-brain connection allows microbiota to shape an organism’s responsiveness to stress. In fact, studies have shown that treatment with gut microbiota Lactobacillus rhamnosus JB-1 was effective in decreasing anxiety-like behavior in rats that were caused by stress (Bharwani, Mian, Surette, Bienenstock, & Forsythe, 2017). Thus, a gut-microbiota-based treatment can indeed reverse the alterations in HPA axis that cause elevated levels of cortisol, which in turn, reduces the symptoms of depression.
Neurotransmitters GABA & Serotonin
A dysfunction in GABA production is often reported in the pathophysiology of various chronic disorders, such as anxiety and major depressive disorder (Rieder, Wisniewski, Alderman, & Campbell, 2017). GABA is an inhibitory neurotransmitter that is responsible for regulating psychological and physiological processes. GABA is known to play a very important role in aiding the brain to control stress, which is a major vulnerability factor in mood disorders.
Interestingly, psychobiotics produce major alterations in the expressions of GABA receptors in the brain. When the structures of the receptors are altered, their functions and pharmacological characteristics also change. Indeed, the exposure to early gut microbiota disturbance decreased the expressions of GABA receptors in the hippocampus (Liang, Zhou, Zhang, Yuan, & Wu, 2017).
The decreased expression of the receptors, particularly the emotional behavior regulating receptors in the hippocampus, creates a deficit in the transmission of GABA. Thus, the deficit of GABA in the hippocampus prevents it from controlling the stress response, leading to depressive symptoms.
Notably, psychobiotics have shown to increase of GABA receptor expression in the hippocampus in an experiment (Burokas et al, 2017). With that being said, psychobiotics can alleviate depressive symptoms by synthesizing GABA in the brain.
In addition, gut microbiota synthesizes serotonin, a neurotransmitter that is typically involved in the regulation of a number of bodily functions. Research indicates that “over 90% of serotonin in the human body is synthesized from tryptophan by enterochromaffin cells of the gut” (Wiley et al, 2017). The synthesis of serotonin in the brain depends on the availability of its precursor, tryptophan. Depressive behaviors are most likely to occur when the availability of tryptophan is inadequate for normal synthesis of serotonin.
Interestingly, gut microbiota regulates plasma tryptophan and hippocampal serotonin, which are typically elevated in germ-free animals. Based on experiments done, it is apparent that psychobiotics normalize these levels (Foster, Rinaman, & Cryan, 2017). It’s worth noting that the symptoms of depression are due to insufficient levels of neurotransmitters, including serotonin (Liang et al, 2018). Thus, psychobiotics can reduce the symptoms of depression by regulating tryptophan expression, which is responsible for serotonin production.
Are Psychobiotics Truly Effective?
Unlike any other treatment method, psychobiotics are “well-adapted to intestinal environment and naturally modulate gut-brain axis, reducing the chance of adverse reactions” (Kali, 2016). Therefore, psychobiotics treat mental disorders effectively and in a healthy way, with almost no side effects. This is one of the many qualities of psychobiotics that further indicates that it has what it takes to be a treatment of value for major depressive disorder.
In a time needed more than ever, psychobiotics are a relatively new subject of interest in research in the field of psychoneuroimmunology and they have proved to be very powerful candidates to treat major depressive disorder. The qualities of psychobiotics, such as its ability to reduce inflammation, its microbial composition’s relationship with mental disorders, and its ability to reduce anxiety-like behavior, qualifies it to become an actual treatment for major depressive disorder.
Psychobiotics are more than just probiotics ingested, they exert powerful antidepressant qualities, especially when ingested in the right, sufficient amount. Considering the increasing prevalence of major depressive disorder and the therapeutic effects of psychobiotics, the addition of psychobiotics to the treatments of mental disorders such as major depressive disorder may be just what is needed to alleviate this epidemic.