The Gut-Brain Connection: The Role of Probiotics in Maintaining Good Mental Health

You Are What You Eat

The human intestine consists of around 100 trillion bacteria that are essential for our health. The connection between the gut and brain has been proven to significantly affect people, especially those suffering from mental illness or other mental health disorders. This connection (known as bidirectional signaling) occurs as neural signals control gastrointestinal functioning; however, signaling from gut microbiota can also affect neurological functioning. Current research on the relationship between the gut and brain could impact those with mental health disorders, particularly the two most-prevalent in the U.S. (anxiety at 16.6% and depression at 28.8%).[1] 

mechanisms in the brain

The primary connection between the gut and brain involves the hypothalamic-pituitary-adrenal (HPA) axis. Through this axis, the gut microbiota can regulate levels of stress hormones such as cortisol. Vagal pathways, which are involved in the activation and regulation of the HPA axis, are the means by which the gastrointestinal tract can activate stress circuits.[2] Probiotics live microorganisms that are administered as dietary supplements or food products for health benefits have the ability to reverse the response of stress hormones being released down the HPA axis.[3] Abnormalities and hyperactivity of the HPA axis have been found to be a possible biological factor of anxiety and depression, along with other neuroanatomical abnormalities in levels of neurotransmitters (i.e., chemical substances that deliver hormonal responses in the brain).[4,5] The HPA axis is also related to depression, as depressive episodes are associated with its dysregulation and the resolution of these depressive episodes are associated with its normalization.[6] Gut microbiota are important in influencing the programming of the HPA axis in the early stages of life as well as in the reactivity of stress throughout life. 

There are several neurotransmitters affected by microbiota strains in the gut, such as norepinephrine, serotonin, and neuroendocrine. Specifically, GABA (4-aminobutanoic acid) is an inhibitory neurotransmitter in the central nervous system (CNS) that works in areas of the brain related to emotion, mood, and memory. Dysfunctions in the signaling of GABA are linked to an increase in anxiety and depression.[7] The probiotic strains of Lactobacilli and Bifidobacteria have been found to act on GABA in a similar way to antidepressants by increasing the production of GABA and reducing anxiety.[8] This demonstrates how gastrointestinal tract microflora can produce chemical changes in the brain that could regulate emotional and sensory reactions. In addition, the bacteria of the gastrointestinal tract influences CNS functioning through the neuronal activation of stress circuits. In terms of serotonin, the serotonergic system is a major component of the pathogenesis of mood disorders. There is a relationship between microbial composition and serotonin signaling, as changes in the microbiota affect the signaling systems of both serotonin and GABA in the CNS. Specifically, probiotics increased levels of tryptophan (serotonin’s precursor) thereby increasing serotonin availability in the same way as the antidepressant citalopram.[9] Wallace & Milev (2017) also showed that the administration of probiotics prevented increases in levels of norepinephrine that are induced by stress. 

the dangers of gut inflammation

The bacterial diversity of the human microbiome and inflammation of the gut have been found to be related to anxiety and depression. Stool samples of those experiencing anxiety and depression had a lower diversity in the composition of the microbial community compared to the control group (i.e., those without anxiety and depression) who had a greater diversity.[10] Microbial composition is influenced by factors such as genetic predisposition, age, nutrition, exercise, stress, and use of antibiotics.[11] In addition, the use of antibiotics has been shown to significantly decrease the microbial number and diversity in the gut.[12] Lee & Kim (2021) found that around 50% of patients with irritable bowel syndrome (IBS) have comorbid depression and/or anxiety disorder, revealing a high correlation between IBS and stress-related mental health disorders.[13] In terms of the relation of stress and probiotics to the gut microbiome, psychological stress is known to increase intestinal permeability, which allows for the entrance of harmful chemicals such as toxins and various forms of waste to enter the gut and bloodstream. The presence of pathogenic bacteria in the gut has been found to increase anxiety-like behaviors. Similarly, infection and inflammation of the gut also increase anxiety-like behaviors, via gut inflammation caused by increased intestinal permeability (i.e., “leaky gut”).[14,15]

Benefits of probiotics

Probiotics reduce intestinal permeability and inflammation by improving the integrity of the gastrointestinal lining.[16] Further, probiotics help prevent bacterial translocation that is associated with anxiety and depression.[17] Treatment of probiotics have been observed to cause a behavioral effect resembling that from the treatment of the antidepressant citalopram. This demonstrates that probiotics may have the ability to act as a form of antidepressant in a more natural way than prescription medication. Studies by Liu et al. (2019) and Chao et al. (2020) have observed lower levels of depression scores in groups that were in the probiotic condition compared to the placebo condition.[18,19] 

The implications for the psychological benefits of probiotics are significant. Given the high prevalence of anxiety and depression, probiotics offer a promising alternative to the administration of antidepressants and other psychological medications.[20] It’s important to note that if someone is currently taking prescription antidepressants, they should not lower or stop taking them unless directed to do so by their prescribing physician. In terms of implementing probiotics into one's lifestyle, significant evidence suggests that the daily consumption of a probiotic supplement can have positive psychological effects such as an increase in better mood, decrease in anxiety, and decrease in depression (particularly since anxiety is often comorbid with major depressive disorder).

beneficial probiotic foods

Alternatively, there are several fermented foods that can be implemented into one’s diet to increase probiotic intake:[21]

  • Yogurt - one of the best sources of probiotics; yogurt is cultured/fermented milk that has been supplemented with active cultures that promote the growth of good bacteria in the gastrointestinal tract

  • Sauerkraut - finely cut raw cabbage that has been fermented by various lactic acid bacteria

  • Kefir - a tart and tangy cultured milk drink packed with various strains of beneficial probiotics and live cultures; healthiest option is the plain flavor as flavored varieties often contain added sugar; can also be added to smoothies

  • Kombucha - probiotic-rich fermented drink made with tea, sugar, bacteria and yeast

  • Kimchi - a spicy Korean condiment packed with lactobacilli (mentioned earlier in the article); a great addition to Asian dishes including rice, stir fries, and barbecued meats

  • Miso soup - miso is fermented soy that contains healthy bacteria

  • Tempeh - a good alternative to meat made with probiotic-rich fermented soybeans; this is also a healthy source of protein, fiber, and antioxidants

It is important to eat a variety of diverse probiotic foods, since each contains different types of probiotic strains, and each have different effects on the body. In addition, moderation is key in terms of probiotics, as over-consumption may lead to side effects such as bloating or digestive problems.[22] 

Before adding any supplements to one’s diet (such as probiotics), it’s always best to consult your primary care physician to inquire if probiotic supplementation will be suitable for you and confirm which dosage might be best in your case. 

Contributed by: Preeti Kota

Editor: Jennifer (Ghahari) Smith, Ph.D.

REFERENCES

1 Liu, R. T., Walsh, R. F. L., & Sheehan, A. E. (2019, April 17). Prebiotics and probiotics for depression and anxiety: A systematic review and meta-analysis of controlled clinical trials. Neuroscience & Biobehavioral Reviews. Retrieved October 6, 2022, from https://www.sciencedirect.com/science/article/pii/S0149763419300533?casa_token=ken0MaMJETEAAAAA%3Azjgy9sFKvv6Yf-7-7w9IIarVfXEeDGX9aYQ21R-cwPTSQnGUVf_R9-3AwXkERA4k5Ymlpgzl

2 KA;, F. J. A. M. V. N. (n.d.). Gut-Brain Axis: How the microbiome influences anxiety and depression. Trends in neurosciences. Retrieved October 6, 2022, from https://pubmed.ncbi.nlm.nih.gov/23384445/

3 Ibid.

4 YK;, L. Y. K. (n.d.). Understanding the connection between the gut-brain axis and stress/anxiety disorders. Current psychiatry reports. Retrieved October 6, 2022, from https://pubmed.ncbi.nlm.nih.gov/33712947/

5 Wallace, C. J. K., & Milev, R. (2017, February 20). The effects of probiotics on depressive symptoms in humans: A systematic review - annals of general psychiatry. BioMed Central. Retrieved October 6, 2022, from https://annals-general-psychiatry.biomedcentral.com/articles/10.1186/s12991-017-0138-2

6 Foster & Neufeld (2013)

7 Ibid.

8 Kane, L., & Kinzel, J. (2018). The effects of probiotics on mood and emotion. JAAPA, 31(5), 1-3. 10.1097/01.JAA.0000532122.07789.f0

9 Wallace, C. J. K., & Milev, R. (2017, February 20). The effects of probiotics on depressive symptoms in humans: A systematic review - annals of general psychiatry. BioMed Central. Retrieved October 6, 2022, from https://annals-general-psychiatry.biomedcentral.com/articles/10.1186/s12991-017-0138-2

10 Lee & Kim (2021)

11 Ibid.

12 Foster & Neufeld (2013)

13 Lee & Kim (2021)

14 Foster & Neufeld (2013)

15 Wallace & Milev (2017)

16 Ibid.

17 Lee & Kim (2021)

18 Liu et al. (2019)

19 Chao, L., Liu, C., Sutthawongwadee, S., Li, Y., Lv, W., Chen, W., Yu, L., Zhou, J., Guo, A., Li, Z., & Guo, S. (1AD, January 1). Effects of probiotics on depressive or anxiety variables in healthy participants under stress conditions or with a depressive or anxiety diagnosis: A meta-analysis of randomized controlled trials. Frontiers. Retrieved October 6, 2022, from https://www.frontiersin.org/articles/10.3389/fneur.2020.00421/full

20 Wallace & Milev (2017)

21 How to get more probiotics. Harvard Health. (2020, August 24). Retrieved October 6, 2022, from https://www.health.harvard.edu/staying-healthy/how-to-get-more-probiotics#:~:text=The%20most%20common%20fermented%20foods,sourdough%20bread%20and%20some%20cheeses

22 Yang, S. (2022, April 22). Why cooking with probiotics might change your gut health for the better. TheThirty. Retrieved October 6, 2022, from https://thethirty.whowhatwear.com/how-to-incorporate-probiotics-into-diet/slide13