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According to the World Health Organization 300 million people have depression and in the US alone 40 million have an anxiety disorder. These disorders affect all aspects of a patient's life and cost the US millions of dollars each year and less than half are seeking treatment. A new approach to this problem is making a connection between intestinal microbiome dysbiosis and these depressed or anxious symptoms. New studies have shown that not only in murine studies, but in human studies there is a positive connection between certain bacteria and mood.
The studies vary greatly in terms of the target mechanism of the microorganisms, this is because depression and anxiety are not completely understood and many first line treatments work on masking symptoms rather than curing the disease. The goal of this review is to examine randomised, double blinded trials that compare general self reported symptoms of these disorders or even characteristics or mechanisms that lead to these disorders pre and post probiotic supplementation.
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According to the data in these studies there is a connection between a specific balance of bacteria in the gut and a decrease in depressive and anxiety symptoms. At some point in an U.S. adults life 21.4% will experience some sort of mood disorder. This creates a huge economic and social burden on the U.S. as well as decrease the quality of life of the patient.
Emerging studies on rats have shown a clear connection between gut microbiota and emotional responses to stressors, however there has been few studies making these connections in humans.
In order to study this connection between the 1013 microorganisms living in our gut and our mood, we need to understand 1) the mechanisms of depression and anxiety and 2) how those microorganisms affect those mechanisms of disease. Many processes within our bodies contribute to mood disorders, but in connection to the microbiome there are three that human studies focus on: systemic inflammation, HPA axis, and direct neuroactive substance created by the microorganisms.
By finding out how exactly the microbiome affects our mood, we can target treatment and prevention methods in order to decrease the diseases’ burden on the community as well as the patient. One thought on the progression of depressed and anxious mood is a heightened response to negative stressors. This is what makes the different from a sad mood as a transient state versus a prolonged state that can lead to clinical depression (Steenbergen, Sellaro, Hemert, Bosch, Colzato,2015). Negative stressors are processed in the amygdala, frontal, and temporal cortices. By measuring the activity in these areas of the brain after a negative or stressful event we can quantify the change in response over time (Pinto-Sanchez et al., 2017). The mechanism of how these areas are activated are not completely understood, however in rat studies it has been shown to travel through the vagus nerve pathway. When the vagus nerve is cut we do not see the improvement of symptoms as we do with those intact vagus nerves (Steenbergen et al, 2015). In humans, one treatment of depression is stimulation of the vagus nerve.
Anatomically, the vagus nerve leads to the raphae nucleus, which is the primary source of serotonin in the human brain. The serotonin life cycle is the target for the current first line drug treatment of depression. Another thought on how the microbiome and the CNS interact is directly through neuroactive substances, primarily studied is serotonin. Tryptophan is a precursor to serotonin and it has been shown that bacteria that thrive in our guts can make tryptophan. It is widely known that a decrease in serotonin can worsen depressive symptoms (Kazemi, Noorbala, Azam, Eskandari, Djafarian, 2018). This is already a target of action for one of the most widely prescribed class of drugs: selective serotonin reuptake inhibitors. Through correcting gut dysbiosis to promote growth of the microorganisms that produce tryptophan, it may be possible to prevent depressive episodes or even treat depressive symptoms without the use of prescription medication.
Many disease processes have been linked to systemic inflammation. Mood disorders are no exception. Studies in humans have shown that injections of cytokines produce depressive like symptoms that are improved with SSRIs, which shows the relation between inflammation and depression. Certain bacteria that reside in the human intestines induce inflammatory responses, while others have anti-inflammatory properties (Messaoudi, 2010). Through balancing the dysbiosis in patients with depression, it may be possible to improve their symptoms. (Naseribafrouei, 2014) Chronic inflammation puts the body through stress. When the body is stressed certain hormones are release to help us cope with the stress, these stress hormones are primarily controlled by the hypothalamus pituitary axis.
Cortisol is primary hormone studied in complex hypothalamus pituitary axis, but it also affects serotonin and norepinephrine levels which are the primary targets of current first line drug treatment for depression and anxiety disorders respectively. Through reducing a patient’s baseline cortisol level we can reduce the stress response, therefore reducing depression and anxiety symptoms (Schmidt et al., 2014). Problem Statement Depression alone is a huge economic burden on the US, each year about 210.5 billion dollars is spent on direct and indirect costs. Not only is it an economic burden but also lowers a patient’s quality of life. Patients can spend many years and possibly hundreds to thousands of dollars finding a way to treat or cope with their mood disorders. Unfortunately in 2016 mood disorders claimed the lives of 44,965 people. Emerging studies in humans are showing that depression can be prevented and possibly even treated with improvement of dysbiosis (Steenbergen et al, 2015).
Mood disorders have a multifactorial etiology including genetics, psychosocial stressors, and neurotransmitter imbalance, and still some aspects leading to depression disorders are still a mystery. Improving one aspect of the etiology does not guarantee a solution, but may reduce the likelihood of developing or lessen the severity of the disorder. Current treatment methods of treatment include learning how to better cope with psychosocial stressors and medications targeted at balancing the neurotransmitters, and still these methods can fall short of full treatment, leading one to believe there is some aspect that we are not addressing currently. Current studies are hypothesizing that by creating a balanced microbiome, we can combat depression better. With increased antibiotic use, the standard American diet, and a multitude of other contributing factors, our society’s microbiomes are not balancing in the way that is optimal for our mental and physical health.
Clinical Review Goal Research goal Through this clinical review we attempt to connect a well balanced intestinal microbiome with decreased incidence or possibly decreased severity of mood disorders. These connections have been made in murine studies, so naturally the next step would to be to ensure these connections are the same in humans and figure out how can we use this information to treat mood disorder (Messaoudi, 2010). Research Question In order understand how a balanced intestinal microbiome can improve or prevent mood disorders we must understand how they develop in the human body. Once it is know how they develop we must ask: How we can alter these pathways or processes to see clinical improvement of symptoms in patients? If it is possible to improve patients symptoms of depression through the proper balancing of microorganisms in the GI tract, what microorganisms are beneficial and which are detrimental to the mental health of a patient?
Finally if we can see clinical improvement of depressive symptoms, is improving gut dysbiosis enough to treat depression, or is it better used as a preventative measure or adjunct to traditional therapy? Relevance and Significance As stated in the sections above, depression and depressive symptoms are on the rise not only in the US but all over the world, currently 300 million people are affected and is the leading cause of disability according to the WHO. If severe enough, depression can ultimately lead to suicide which is the second leading cause of death in people age 15-29 years old. Although everyone with depression may not seek treatment, globally, almost half are receiving some sort of treatment, and still it remains a huge burden on society. So what can be done to reduce the burden and improve patient’s quality of life?
There are many factors leading to depression and many pathways within the body that work on these symptoms, so it is hard to target just one thing to study and try to improve. So a smart place to start would to address the factor that has changed the greatest amount in the shortest amount of time, and that is the human diet and its effect on the microbiome. Current accepted treatment methods include talk therapy which target connections within the brain associated with reactivity to negative or stressful situations, and medications which target the neurotransmitter imbalances thought to contribute to the symptoms of depression. However, these efforts are not enough since the burden is still so high, and the patient becomes dependent on the medication or must actively train to “rewire” how the brain reacts to situations through therapy.
These reasons contribute to the non-compliance with treatment and unsuccessful attempts to remit the depressive symptoms. If a patient could shift the microorganisms in their GI tract to benefit them better they may not need to take a drug daily, or at least have a greater improvement of symptoms while taking an antidepressant. Studies looking at the gut-brain axis are still in infancy, so the information available is very general and aims on providing sure connections between the two, rather than describing concrete changes to depression symptoms. We know there is a connection between mood and our microbiomes, however we do not know what these connections are for sure.
Many of the studies in this paper deal with self reported clinical changes before and after treatment, but the newer studies are focusing more on what these connections are and how different bacteria or organisms affect the pathways. By finding out how these pathways interact with the microbiome more definitive studies can take place. One day soon we can be studying dosing of different probiotics that improve depressive symptoms versus those that may improve anxiety symptoms. We may be able to go as far as to developing a diet to improve these symptoms, which may even eliminate the need to treat depression and anxiety with the traditional psychotherapy and antidepressant or anti-anxiety medications.
Importance of Intestinal Microbiota Effects on Mood . (2022, Apr 06). Retrieved from https://studymoose.com/importance-of-intestinal-microbiota-effects-on-mood-essay
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