Microbiota: Leveraging the body’s gut microbiome to treat depression
Depression is common. According to estimates from the World Health Organization (WHO), about 280 million people worldwide have depression. However, the current treatment strategies are inefficient with the treatment not working for 30% or 84 million people.
Why?
The current solution for depression is based off of the “neurotransmitter hypotheses of depression”; this entails that an imbalance in neurotransmitter levels is what causes symptoms of depression. First off, what are neurotransmitters?
Neurotransmitters are chemical messengers that your body can’t function without. These messengers carry chemical signals from one nerve cell to the next target cells. Target cells could include another nerve cell, a muscle cell or a gland. This process can influence mood, and this is how it correlates to depression.
An imbalance in neurotransmitters can lead to mood swings and depression. This has been proved through various studies which looked at differences in mood between people with imbalances in neurotransmitter levels and without. For example, for the neurotransmitter serotonin, this has been proved through a study where they used acute dietary manipulations to produce a transient lowering in brain serotonin levels and monitored resulting changes. What researchers found, is that patients had significant changes in mood, and many had symptoms of depression.
While a lot of research is needed to solidify this hypothesis, current research prove that an imbalance of different neurotransmitters including, GABA, glutamate, norepinephrine, dopamine and serotonin can cause one to experience depression.
Connection to the Gut Microbiome
These give neurotransmitters have been strongly linked to depression and an imbalance can lead to anxiety and stress like symptoms. The gut microbiota has a variety of bacteria which have the ability to influence the production of these neurotransmitters. For example, Enterococcus has shown the ability to produce serotonin. Furthermore, majority of the neurotransmitters in the body are made in the gut; 95% of the body’s serotonin is made in the gut.
Our Solution
Now that we understand that is an imbalance in neurotransmitters that has proved to be a significant cause for depression, we can use this information to determine how to progress with a patient after their initial diagnosis. By testing ones neurotransmitter levels, we can begin with the treatment to correct the imbalance.
As neurotransmitters circulate in the blood and are filtered out by the kidneys via urine, a neurotransmitter test, taken from the urine, is an accurate and non-invasive way of measurement. The ability to test neurotransmitter levels from the urine is not something researchers dispute over as there have been studies demonstrating renal transporters capable of filtering neurotransmitters from the blood to the urine. We will be looking for the levels of five key neurotransmitters: GABA, glutamate, serotonin, dopamine, and norepinephrine.
We plan to use oral medication which will allow us to manipulate the bacteria in the gut microbiota and rebalance the levels of any given neurotransmitters. This oral medications will be using probiotics; the probiotics will work to increase a certain strain of bacteria in the gut. Typically depression is caused by a depletion in neurotransmitters; hence, we don’t need to focus on decreasing specific strains of bacteria.
Probiotics are often sold in various drug store marts, but we will be focusing our medication on one bacteria strand. For example, if we wanted to increase the strain of E. Coli in someones microbiota, we would be sending the live bacteria through the medication to increase the population. While it can be hard for bacteria to survive the harsh conditions of stomach acid, our choice in which bacteria will be significantly important. Furthermore, we will also be limited to which bacteria we can use as we cannot administer most gram-negative bacteria as it can lead to an infection. The LPS or liposaccharides found in the outer membrane of Gram-negative bacteria can start an immune system attack when found in large numbers in the blood and can eventually lead to sepsis. Once we chose which bacteria strain the patient needs, we will then grow, ferment, concentrate in a centrifuge and blend the bacteria.
Anti-microbial peptides are diverse and bioactive compounds that play a huge role in maintaining tolerance to commensal microorganisms like bacteria. This essentially means that by administering these peptides through an oral pill we can control the growth of certain bacteria in the gut microbiota.
Here is a chart of how we will influence a change in the 5 main neurotransmitters through peptides and probiotics, as well as which medication will be influencing which bacteria.
How that we have balanced the neurotransmitter levels in the body, we have to get them to the brain by getting through the BBB (blood brain barrier). We can do this by using microbubbles in a solution diluted with physiological saline. These microbubbles can be safely injected intravenously, and once they reach the blood-brain barrier the focused ultrasound makes the bubbles expand and contract within the blood vessels. This makes them temporarily more permeable, allowing drug molecules in the blood to pass into brain tissue.
While this process hasn’t been fully developed, we can foresee it to be avalible in the next 10 years as the technology has been approved for echocardiologies in certain cases proving its efficacy. As microtubles move onto clinical trials in humans into the coming years, we predict it will be implementable in our process.
Starting from the inside
Our method provides individuals relief without adverse long-term effects through leveraging the gut. Unlike current medication, we don’t provide a temporary solution, rather a flourishing microbiota that is self-preserving in tackling depression. In addition, this solution mitigates the impact of withdrawal and addiction. Our natural solution doesn’t directly impact the neurotransmitters, rather leverages your own body to balance neurotransmitter levels. Microbiota targets depression using our body’s very own population — the gut microbiota.
