A Quick Breakdown of The Role of Gut Microbiomes in Mental Health Disorders

It may seem like our gut has nothing to do with our brain, but you’ll be surprised to find several links between the two parts of our body. Gut microbiota plays a key role in mental health disorders and this article will be going over a few ways our gut influences common neurological disorders.

Gut microbiota is comprised of bacteria, yeasts, and viruses that are often involved in human biological processes, like nutrient extraction, metabolism, and immunity [1]. The main bacteria you would find in the gut environment are anaerobic bacteria like Bacteroidetes and Firmicutes [1]. More importantly, it is closely related to the development of diseases because when an external factor enters our body, the balance and state of our gut microbiome changes [1]. As a result, our bodily processes, such as our immune system, are affected, leading to diseases or disorders emerging [1].

The gut-brain axis is the bidirectional communication between the central nervous system and the enteric nervous system, which controls our gastrointestinal functions [2]. Communication methods between our gut and brain can be direct or indirect. Direct pathways refer to neuroanatomical connections like the vagus nerve, pelvic splanchnic nerve, and some sympathetic nerve branches [3]. The vagus nerve is ultimately the quickest path between the two parts, starting from the brain stem and traveling down through the neck and towards the gut [3]. On the other hand, indirect communication systems have to do with chemical signaling [3]. For example, short-chain fatty acids (SCFAs) produced by gut microbes influence neuroplasticity, epigenetics, and gene expression [3]. When microbial metabolites stimulate enteroendocrine cells, the serotonin neurotransmitter is released [3]. Other microorganisms, including Bifidobacterium, Bacteroides, Parabacteroides, etc. can produce GABA neurotransmitters [3]. Furthermore, gut microbes can create cytokines (signaling proteins involved in the immune system) that can enter the central nervous system through the blood-brain barrier [3]. 

When we have a healthy gut, we likely have a properly functioning central nervous system. However, when things like diet changes, stress, or antibiotics start to disrupt our gut microbiome, it enters a dysbiotic state (unbalanced state) where intestinal permeability increases, letting bacterial metabolites and other larger molecules in [4]. This increased permeability negatively affects our immune system, leading to diseases like inflammatory bowel disease, diabetes, and asthma [4]. But more importantly, neurological disorders like depression, anxiety, and autism arise because, with a more permeable intestine, we see elevated blood levels of the cytokines TNF-a and MCP which prompt the blood-brain barrier to be more penetrable as well [4]. Inflammation in the gastrointestinal tract releases excessive cytokines and neurotransmitters that put further stress on our microbiome [4]. The release of these molecules leads to anxiety, depression, and memory loss [4]. 

Moreover, pro-inflammatory cytokines can stimulate the hypothalamic-pituitary-adrenal axis, which lets out the corticotropin-releasing factor [4]. This triggers the adenohypophysis to release adreno-corticotropic hormone (ACTH), which in turn releases cortisol – a major stress hormone [4]. 

Bipolar disorder is usually associated with a less diverse gut microbiota but a greater abundance of Clostridiaceae and Collinsella [5]. Some studies also found increased levels of Actinobacteria and Coriobacteria [6]. Other studies determined a decreased amount of Faecalibacterium and Ruminococcaceae [6]. However, it is important to note that most of these studies dealt with a small group of patients which may not accurately represent the whole population. Further large-scale research is needed to confirm these claims. 

Schizophrenia, a rare and serious mental disorder, is characterized by a few special types of gut bacteria found uniquely in schizophrenia patients: Lactobacillus fermentum, Enterococcus faecium, and Alkaliphilus oremlandii [7]. A cross-sectional study also discovered some gut bacteria, like Haemophilus, that were missing in schizophrenia patients but existed in healthy individuals [8]. It is possible to use this research to produce therapy treatments for mental disorders like schizophrenia. In this case, we can target the beneficial gut bacteria that is missing in schizophrenia patients and flush out the harmful gut bacteria found exclusively in those with schizophrenia [6]. 

Our understanding of the gut-brain axis and the gut microbiome’s relationship with our nervous system is still heavily undeveloped. More research with larger samples can help confirm results and answer more specific questions about our gut’s impact on our brain. While the opportunities to learn more about these areas of our body are endless, this topic encourages us to incorporate a more holistic approach to treating mental disorders, considering how other organs factor into our thought processes and moods.

Works Cited

1. Hou, K., Wu, ZX., Chen, XY. et al. Microbiota in health and diseases. Sig Transduct Target Ther 7, 135 (2022). https://doi.org/10.1038/s41392-022-00974-4 
2. Rao, M., Gershon, M. The bowel and beyond: the enteric nervous system in neurological disorders. Nat Rev Gastroenterol Hepatol 13, 517–528 (2016). https://doi.org/10.1038/nrgastro.2016.107
3. Han, Y., Wang, B., Gao, H., He, C., Hua, R., Liang, C., Zhang, S., Wang, Y., Xin, S., & Xu, J. (2022). Vagus Nerve and Underlying Impact on the Gut Microbiota-Brain Axis in Behavior and Neurodegenerative Diseases. Journal of inflammation research, 15, 6213–6230. https://doi.org/10.2147/JIR.S384949
4. Clapp, M., Aurora, N., Herrera, L., Bhatia, M., Wilen, E., & Wakefield, S. (2017). Gut microbiota’s effect on mental health: The gut-brain axis. Clinics and practice, 7(4), 987. https://doi.org/10.4081/cp.2017.987
5. McIntyre, R. S., Subramaniapillai, M., Shekotikhina, M., Carmona, N. E., Lee, Y., Mansur, R. B., Brietzke, E., Fus, D., Coles, A. S., Iacobucci, M., Park, C., Potts, R., Amer, M., Gillard, J., James, C., Anglin, R., & Surette, M. G. (2021). Characterizing the gut microbiota in adults with bipolar disorder: a pilot study. Nutritional neuroscience, 24(3), 173–180. https://doi.org/10.1080/1028415X.2019.1612555
6. Xiong, R. G., Li, J., Cheng, J., Zhou, D. D., Wu, S. X., Huang, S. Y., Saimaiti, A., Yang, Z. J., Gan, R. Y., & Li, H. B. (2023). The Role of Gut Microbiota in Anxiety, Depression, and Other Mental Disorders as Well as the Protective Effects of Dietary Components. Nutrients, 15(14), 3258. https://doi.org/10.3390/nu15143258
7. Zhu, F., Ju, Y., Wang, W., Wang, Q., Guo, R., Ma, Q., Sun, Q., Fan, Y., Xie, Y., Yang, Z., Jie, Z., Zhao, B., Xiao, L., Yang, L., Zhang, T., Feng, J., Guo, L., He, X., Chen, Y., Chen, C., … Ma, X. (2020). Metagenome-wide association of gut microbiome features for schizophrenia. Nature communications, 11(1), 1612. https://doi.org/10.1038/s41467-020-15457-9
8. Manchia, M., Fontana, A., Panebianco, C., Paribello, P., Arzedi, C., Cossu, E., Garzilli, M., Montis, M. A., Mura, A., Pisanu, C., Congiu, D., Copetti, M., Pinna, F., Pazienza, V., Squassina, A., & Carpiniello, B. (2021). Involvement of Gut Microbiota in Schizophrenia and Treatment Resistance to Antipsychotics. Biomedicines, 9(8), 875. https://doi.org/10.3390/biomedicines9080875