There is bidirectional communication between the gut and the brain. In fact, reputable scientists such as Dr. Michael Gershon, professor of Pathology and Cell Biology and father of neurogastroenterology, adamantly believe that we have a second brain in our gut.
The human gut is lined with more than 100 million nerve cells, more than in the spinal cord or in the peripheral nervous system. Yes, we have brain cells in our large intestines! This explains why antibiotics which disturb the gut microbial ecosystem might cause neuropsychiatric effects, interact with psychotropic medications, and/or influence our mood (1). This also explains why mood disorders are so prevalent in patients with irritable bowel syndrome (2).
Chemicals implicated in depression and happiness such as serotonin are also found in the gut; 90 percent of serotonin is manufactured in the digestive tract and not the brain. Many antidepressants work by increasing serotonin. Scientists have found that gut bacteria produce many other neurotransmitters such as dopamine, norepinephrine, acetylcholine, and GABA, which are critical for mood, anxiety, concentration, reward, and motivation. The gut microbiome can cause changes in how our brains react.
In a UCLA study, a group of healthy women with no gastrointestinal or psychiatric symptoms were randomly assigned to one of three groups: fermented milk product with probiotics "yogurt," a non-fermented milk product (with a probiotic containing a consortium of five strains), or no intervention. They consumed this twice daily for four weeks.
Researchers collected brain images before and after the intervention to look for any brain changes in response to an emotional attention task. They also collected stool samples. The results were astonishing—there were significant differences in how the brains reacted during the emotional task! The group of women who consumed fermented milk for only four weeks had calmer brains during the emotional task! The no-intervention (no yogurt) group showed the opposite trend, more brain hyperactivity during the emotional task. (3)
Exposure and consumption of good bacteria are necessary for a balanced brain. Studies found that in germ-free sterile mice, there is an imbalance of depression-related brain chemicals in areas important for emotions and mood. Also, there are significantly more pro-inflammatory cytokines in depressed people compared to non-depressed ones. This effect on the inflammatory system may stem from interactions with a dysfunctional gut microbiome in depressed individuals.
Also, stress makes us more likely to develop mood disorders. And stress makes the gut more permeable to bacteria. Reciprocally, depression causes dysbiosis—an imbalance of good to bad gut bacteria. In sum, depression is maybe caused by dysfunctional gut-brain-immune system interactions.
Good gut bacteria or the absence of some bad ones can make us more resilient to depressive states after stressors or trauma. It is not surprising that chronic exposure to stress is associated with a higher incidence of depression, anxiety, and PTSD. But not everyone who faces stress develops a mood disorder, and not everyone who experiences a trauma develops PTSD.
Resiliency, the ability to recover quickly from difficulties, is maybe a function of what bacteria lives or does not live in your gut. In one study, they found that vulnerable rats who showed depression-like behaviors also exhibited inflammation in the hippocampus. But the gut microbiome is in constant interaction with inflammatory substances.
Indeed, the fecal microbiome of vulnerable rats contained more immune-modulating microbiota (gut microorganisms) such as Clostridia compared to resilient rats. When microbiota from the vulnerable rats was transferred to resilient rats, they displayed depressive behaviors. This evidence fortifies the link between gut bacteria and depression. (4)
How can lowly gut bacteria down there affect higher functions up there in the brain? How can unintelligent, simple organisms affect behaviors, thoughts, and actions of our intellect? These microbiotas have several strategies to affect our brains and therefore minds. One that has already been mentioned above is that gut bacteria produce neurotransmitters that are important for behaviors, mood, thoughts and other cognitive abilities.
Also, some microbiota can change how these brain chemicals get metabolized in the body and thus determine how much is available for action in blood circulation. Other chemicals generated by gut bacteria are called neuroactive, such as butyrate, which has been shown to reduce anxiety and depression. Another pathway is the vagus nerve which is one conduit for the bidirectional gut-brain communication (5). The immune system is yet another one. The immune system is intimately connected to the gut microbiome and the nervous system, and thus can be a mediator of the gut’s effects on the brain and the brain’s effects on the gut.
Not only have many studies across many laboratories showed evidence for brain-gut interactions, but scientists have also cataloged specific bacteria as they relate to various states of mental health. In a large population study (part of the Flemish Gut Flora project), researchers investigated the correlation between microbiome factors and quality of life and depression. Not only did they find a link between the gut microbiome and mental health, but they were able to catalog the exact names of bacteria associated with good and bad quality of life. (6)
What has become evident is that patients with psychiatric disorders have different populations of gut microbes compared to microbes in healthy individuals. Also, stress and stress hormones such as cortisol can have a negative impact on our microbiome. And all of these factors interact in complex ways with the immune system.
As the knowledge of the exact nature of brain-gut interactions unfolds in relation to psychiatric disorders, treatments may include a probiotic instead of Prozac! What all of the above findings strongly suggest is this: Take care of your gut bacteria for good quality of life, better mental health, and a sharper brain.
(1) Sternbach H, State R. Antibiotics: neuropsychiatric effects and psychotropic interactions. (1997). Harv Rev Psychiatry; 5: 214–226.
(2) Whitehead WE, Palsson O, Jones KR. Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications? (2002). Gastroenterology, 122: 1140–1156.
(3) Tillisch, K., Labus, J., Kilpatrick, L., Jiang, Z., Stains, J., Ebrat, B., … Mayer, E. A. (2013). Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology, 144(7), 1394–1401.e14014. doi:10.1053/j.gastro.2013.02.043
(4) Pearson-Leary, J., Zhao, C., Bittinger, K., …Bhatnagar, S. (2019). The gut microbiome regulates the increase in depressive-type behaviors and in inflammatory processes in the ventral hippocampus of stress vulnerable rats. Molecular Psychiatry. https://doi.org/10.1038/s41380-019-0380-x
(5) Bravo, J. A., Forsythe, P., Chew, M.V., …Cryan, J.F. (2011). Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. PNAS, 108(38), 16050-16055. https://doi.org/10.1073/pnas.1102999108
(6) Valles-Colomer, M., Falony, G., Darzi, Y., ... Raes, J. (2019). The neuroactive potential of the human gut microbiota in quality of life and depression. Nature Microbiology, 4, 623-632.