Faced with important decisions, we often listen to what our “gut” is telling us, believing that our true intuition originates from somewhere deep within.
There is indeed truth to this feeling. The brain has long been considered the source of our cognition and the control center of our body. However, modern science has confirmed that our gut, or gastrointestinal (GI) tract, might be just as influential in how we think and feel.
A "Gut Feeling"
Dual Brains
The “second brain” theory [1] suggests that we actually have two “brains,” one in our head and one harbored within our gut. In addition to our central nervous system (CNS), which is comprised of our brain and spinal cord, our GI tract has its own independent neural network. During embryonic development, both systems originate from the same tissue and remain physically linked together throughout life by the vagus nerve. This gut-brain axis (GBA) involves both “brains” functioning independently, yet still maintaining constant, bidirectional communication.
The Gut Microbiome
Gut microbiota are the thousands of species of microorganisms living inside our GI tract. They can outnumber the human cells in our body and weigh as much as our own brain. This environment - composed of our own epithelial, immune, and nerve cells; enteric microbes; and a countless range of molecules - is our gut microbiome.
This microbiome is responsible for much of our gut-brain messaging, and its biotic diversity profoundly influences our health. These gut microbes induce communication between our two “brains” using molecules such as neurotransmitters, hormones, fatty acids, and other metabolites.
Microbiota-Gut-Brain Pathways
Our gut microbiota-gut-brain axis functions bi-directionally, with the enteric microbiome neurons in constant interaction with our CNS. The following are some of the mechanisms by which this communication occurs.
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Immune system
Microbes in the gut can induce immune cells within the intestine to secrete a range of cytokines. These circulate via the bloodstream throughout the body. Though typically not able to pass directly into the brain, cytokines are still able to stimulate neurological responses through interaction at weaker, more susceptible regions of the blood-brain barrier (BBB).
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Vagus nerve
The vagus nerve runs from the brain to the gastrointestinal tract, a direct communication pathway between the CNS and the gut. A 2011 study in mice [6] found that only when the vagus nerve was intact did a specific B. longum strain show an anxiolytic effect in mice with induced colitis; post-vagotomy, the probiotic-treated mice behaved no differently than a control group.
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Metabolites
Gut microbiota can help generate the precursors of neurotransmitters and other metabolites. These circulate through the bloodstream, and some, such as short-chain fatty acids, even pass directly through the BBB.
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Endocrine
The hypothalamic–pituitary–adrenal (HPA) axis is another key pathway of microbiota-gut-brain interaction. Upon feeling stress, the HPA axis stimulates the adrenal gland to secrete cortisol (stress hormone), which causes a sympathetic nervous system “fight or flight” response. Multiple body systems are either triggered or demobilized in order to react effectively to the external situation. Certain microbes in our gut can directly reduce circulating cortisol levels. Normalization of this stress hormone has the effect of reversing the HPA axis feedback loop to the brain, which diminishes secretion of the hormone and further lowers its concentration.
PS128: Nervous System Regulation
Certain neurotransmitters known to directly affect our mood are often referred to as happy hormones. Dopamine and serotonin are two of the most influential of these.
Proper regulation of these hormones is necessary for mental health and overall wellbeing. Their imbalance can result in a wide range of mental, emotional, and physical disorders, from depression or autism spectrum disorder to insomnia or Parkinson’s disease.
More Happy, Less Stress
Preclinical studies [7][8] have demonstrated PS128’s ability to modulate dopamine and serotonin, as well as the primary stress hormone, corticosterone (cortisol in humans). This is likely carried out via one or more of the pathways described above. PS128 was found to raise the concentration of happy hormones dopamine and serotonin in most situations, while effectively reducing stress hormone levels. As a result, laboratory mice were found to respond better in stressful situations.
serotonin
dopamine
PS128 modulates happy hormones
cortisol
PS128 balances stress hormone
The Gut-Brain-Axis and Neurological disorders
As we explore the Gut-Brain Axis (GBA), probiotic strains like PS128 emerge as potential solutions for neurological disorders, including Autism Spectrum Disorder (ASD), Parkinson's Disease (PD), and Major Depressive Disorder (MDD).
In ASD and PD, neuroinflammation is a key factor. It refers to inflammation affecting both the central nervous system (CNS) in the brain and the enteric nervous system (ENS) in the gut. Research shows that children with autism often exhibit elevated immune responses and proinflammatory markers in the brain. Many with ASD also experience gut dysbiosis, contributing to ENS neuroinflammation. PD involves neuroinflammation targeting dopaminergic neurons, leading to neuronal cell death and reduced dopamine levels, causing motor control deficits. ENS neuroinflammation also contributes to non-motor symptoms like constipation.
Laboratory studies have demonstrated that PS128 significantly improves symptoms associated with ASD, PD, and depression in disease mouse models. There is solid evidence suggesting that the consumption of this probiotic could increase dopamine and serotonin levels in the brain while decreasing cortisol. These preclinical findings offer hope for potential benefits in humans, where effective randomized, placebo-controlled trials have already been conducted, showing promising results for individuals with these neurological disorders.
[1] Gershon, M. D. (1999). The second brain: a groundbreaking new understanding of nervous disorders of the stomach and intestine. 1st HarperPerennial ed. New York, NY: HarperPerennial.
[2] Foster, J. A., & McVey Neufeld, K. A. (2013). Gut-brain axis: how the microbiome influences anxiety and depression. Trends in neurosciences, 36(5), 305–312.
[3] Dinan, T., Stanton, C., & Cryan, J. (2013). Psychobiotics: A Novel Class of Psychotropic. Biological Psychiatry, 74, 720-726.
[4] Savignac, H. M., Kiely, B., Dinan, T. G., & Cryan, J. F. (2014). Bifidobacteria exert strain-specific effects on stress-related behavior and physiology in BALB/c mice. Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society, 26(11), 1615–1627.
[5] Allen, A. P., Hutch, W., Borre, Y. E., Kennedy, P. J., Temko, A., Boylan, G., Murphy, E., Cryan, J. F., Dinan, T. G., & Clarke, G. (2016). Bifidobacterium longum 1714 as a translational psychobiotic: modulation of stress, electrophysiology and neurocognition in healthy volunteers. Translational psychiatry, 6(11), e939.
[6] Bercik, P., Park, A. J., Sinclair, D., Khoshdel, A., Lu, J., Huang, X., Deng, Y., Blennerhassett, P. A., Fahnestock, M., Moine, D., Berger, B., Huizinga, J. D., Kunze, W., McLean, P. G., Bergonzelli, G. E., Collins, S. M., & Verdu, E. F. (2011). The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication. Neurogastroenterology and motility: the official journal of the European Gastrointestinal Motility Society, 23(12), 1132–1139.
[7] Liu, W. H., Chuang, H. L., Huang, Y. T., Wu, C. C., Chou, G. T., Wang, S., & Tsai, Y. C. (2016). Alteration of behavior and monoamine levels attributable to Lactobacillus plantarum PS128 in germ-free mice. Behavioural brain research, 298 (Pt B), 202–209.
[8] Liu, Y. W., Liu, W. H., Wu, C. C., Juan, Y. C., Wu, Y. C., Tsai, H. P., Wang, S., & Tsai, Y. C. (2016). Psychotropic effects of Lactobacillus plantarum PS128 in early life-stressed and naïve adult mice. Brain research, 1631, 1–12.