Ishtiak Ahmed Chowdhury

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. 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. Since the gut is responsible for producing over 90% of the body’s Serotonin and is also responsible for the smooth operation of several other neuroimmune, neuroendocrine and sensory-neural pathways, inflammation 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. The disparity in the gut composition of bacteria between healthy and depressed patients is evident in several studies, which 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 has been found to be 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, many of which are implicated 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. This attributes to a vicious cycle that produces a glut of exacerbatory cytokines that worsen the symptoms of depression. 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. 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. 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).

Research also suggests that people with depression have a stronger reaction to the toxins produced by several 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. Additionally, more recently, a decrease in ACE2 expression was observed in murine studies and in silico analyses suggesting that this results in 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.

References:

Butler MI, Mörkl S, Sandhu KV, Cryan JF, Dinan TG. The Gut Microbiome and Mental Health: What Should We Tell Our Patients?: Le microbiote Intestinal et la Santé Mentale : que Devrions-Nous dire à nos Patients? Can J Psychiatry. 2019 Nov;64(11):747-760. doi: 10.1177/0706743719874168. Epub 2019 Sep 17. PMID: 31530002; PMCID: PMC6882070.

Clapp M, Aurora N, Herrera L, Bhatia M, Wilen E, Wakefield S. Gut microbiota’s effect on mental health: The gut-brain axis. Clin Pract. 2017 Sep 15;7(4):987. doi: 10.4081/cp.2017.987. PMID: 29071061; PMCID: PMC5641835.

Hu S, Chen Y, Chen Y, Wang C. Depression and Anxiety Disorders in Patients With Inflammatory Bowel Disease. Front Psychiatry. 2021 Oct 8;12:714057. doi: 10.3389/fpsyt.2021.714057. PMID: 34690829; PMCID: PMC8531580.

Penninger JM, Grant MB, Sung JJY. The Role of Angiotensin Converting Enzyme 2 in Modulating Gut Microbiota, Intestinal Inflammation, and Coronavirus Infection. Gastroenterology. 2021 Jan;160(1):39-46. doi: 10.1053/j.gastro.2020.07.067. Epub 2020 Oct 30. PMID: 33130103; PMCID: PMC7836226.

Rogers GB, Keating DJ, Young RL, Wong ML, Licinio J, Wesselingh S. From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways. Mol Psychiatry. 2016 Jun;21(6):738-48. doi: 10.1038/mp.2016.50. Epub 2016 Apr 19. PMID: 27090305; PMCID: PMC4879184.