Elucidating the Link Between the Microbiome and Depression

By Liza Casella

You probably think of yourself as a single organism—humans are notorious for our human-centric way of seeing the world. But you wouldn’t be the same without your microbiome. The word “microbiome” has recently become a buzzword in the scientific community, and for  good reason. The term refers to the trillions of bacteria that have a symbiotic relationship with their host. While bacteria inhabit nearly every organ in our body, the vast majority of these microorganisms live in our large intestine. It has been known, for many years, that the gut microbiome is necessary for proper digestion, nutrient uptake, and regulation of the immune system. Recent studies, however, have suggested that the microbiome is involved in the development of mental illnesses, as well. 

The brain and intestines communicate through the gut-brain axis, the bidirectional system of communication between the central nervous system and various microorganisms (such as intestinal bacteria, viruses, and unicellular eukaryotes). Intestinal microbes release various hormones, neurotransmitters, and chemicals associated with the immune system. These molecules travel through blood vessels, sending signals to the brain that affect the concentrations of cortisol, dopamine, serotonin, and other neurotransmitters in the blood. While details of the specific mechanisms underlying the gut-brain axis are still unclear, researchers have hypothesized that when the brain experiences emotional stress, intestinal permeability is affected. This leads to not only a reduction in the body’s uptake of nutrients but also to changes in the signaling activity of intestinal bacteria. 

While the discovery of antibiotics, antiseptics, and on the most basic level, soap, in the past few decades has improved general hygiene, it has also led to an unforeseen negative consequence on the microbiome population. These developments have diminished the number of bacteria we come into contact with, reducing the diversity of our intestinal microbiomes. The Hygiene Hypothesis theorizes that this disruption of our microbiomes causes many health conditions such as inflammatory diseases, which were once prevented by intestinal microbes that would in turn activate certain genes for the benefit of human health. 

The link between emotions and the microbiome is clear; when an individual experiences profound stress or sadness, their cells secrete inflammatory cytokines, small molecules that cause an inflammatory response. The process starts in the gut when intestinal microbes interact with receptors on immune cells, triggering an immune response. Then, these microorganisms in the gastrointestinal tract produce neuroactive substances like neurotransmitters which act via the gut-brain axis to affect the central nervous system. Now, researchers have begun testing whether this connection can be extended to potential treatments for mental illnesses such as depression. Depressive disorders are some of the most common mental illnesses, affecting 16.2 million adults in the United States in 2016, primarily between the ages of 18 and 24. Antidepressant medications are currently the most common treatment for these illnesses. Some antidepressants work by increasing the production of immunomodulatory cytokines, which block inflammatory cytokines that cause depression.

Interestingly, similar to antidepressant medications, intestinal bacteria can also elicit the production of immunomodulatory cytokines that travel through the bloodstream and modulate the inflammatory response. However, few studies have been conducted to test the effects of probiotics, or bacteria that we know are beneficial to the microbiome, on alleviating symptoms of depression. A 2015 study found that a multispecies probiotic had a significant effect on improving mood and decreasing aggressive thoughts in a sample of people without current mood disorder diagnosis. While this is an important finding, it does not tell us if probiotics will have the same effect in people with mood disorders. For instance, a 2018 meta-analysis of studies found that probiotic use had an insignificant effect on mood but was limited by the fact that different trials used a variety of different probiotics. Far fewer studies have been conducted using participants who have clinically diagnosed depression or other mood disorders. 

Unfortunately, this limits the extent to which findings demonstrate the effect of probiotics on the mental health of people with mood disorders. Studies should be designed to yield more applicable potential treatments for depression and other mood disorders, which will require including people with mood disorder diagnoses. Because microbiome health may be linked to a variety of mental illnesses, it is important to determine how and if microbes affect brain function, and if probiotics can offer a new treatment option for depression and other mental health disorders. 

We as humans live in symbiosis with our intestinal bacteria. Our health affects theirs and vice versa. Understanding the mechanism by which microbiome health is linked to not only physical but mental health is critical to understanding how mental illnesses arise and develop and to finding an effective treatment. 

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