This article is a part of a series of four articles: “Gut Microbiome and Mental Health.” In this series, we will explore the scientific evidence that specifically points to the association of depression and mood disorders with gut microbiome dysbiosis.
The gut microbiome is one of the most crucial components for healthy living and survival. Hence, any sudden change in the composition of gut flora can have a detrimental consequence on the human body, especially on mental health.
Research shows that any change in the gut microbiome can cause the production of lipopolysaccharide, which causes inflammation in the gut. The gut is responsible for producing over 90% of the body’s Serotonin. Accordingly, it is also responsible for the smooth operation of several other neuroimmune, neuroendocrine and sensory-neural pathways. Hence, inflammation in the gut can cause severe disruption in such pathways leading to deteriorating sleep cycles and mood disorders.
One of the most prominent consequences of such disruption is depression. Therefore, the disparity in the gut composition of bacteria between healthy and depressed patients is evident in several studies. The studies clearly show that Firmicutes, Actinobacteria, and Bacteroides are present in the gut of depressed patients. Hence, “dysbiosis” or a disruption in the population of gut microflora was statistically significant in causing behavior-altering effects in patients with deteriorating mental health. The presence of these microbes stimulates the pro-inflammatory signaling pathways and cytokines. In fact, many of these microbes have severe consequences in patients with depression. For instance: IL-6, CXCL-10, IFN-G, TNF-a, etc. are among some of the inflammatory cytokines that have been associated with depression resulting from inflammation in the gut.
Prolonged neuroinflammation affects brain function and elicits variegated stressors that are not endemic to our bodies. Therefore, this attributes to a vicious cycle that produces a glut of exacerbatory cytokines that worsen the symptoms of depression. However, poor dietary habits, lack of exercise, and stressful events, are all situations that can exacerbate the symptoms of mood disorders and depression in the affected individuals. Moreover, people with IBD are extremely prone to depression since immune-inflammatory, oxidative and nitrosative pathways are involved, which produce pro-inflammatory cytokines.
In patients with MDD (Major Depressive Disorder), dysbiosis can lead to a lower capacity to metabolize carbs and a higher capacity to metabolize protein. Consequently, this has been associated with pathogenesis in MDD patients and a lower abundance of short-chain fatty acids in the body, which could lead to low energy, anxiety, and depression among patients with Major Depressive Disorder (MDD).
However, research suggests that people with depression have a stronger reaction to the toxins produced by bacteria not innate to the gut microbiome. For instance, Morganella and related gram-negative bacteria induce a stronger immune response, and such immune response has been recently associated with the worsening of symptoms of depression. In addition, a decrease in ACE2 expression was observed in murine studies and in silico analyses suggesting decreased tryptophan absorption. A decrease in ACE2 expression disrupts the gut microbiome which in turn results in gut-brain-axis disruption and potentially causes mood disorders.
Ishtiak Ahmed Chowdhury
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