• Karla Benzl, M.D.

Can your microbiome influence your brain?

Updated: Nov 11, 2018

These days, probiotics are all the rage within health food stores and wellness circles. Multiple health claims are made by probiotic manufacturers, including gut health, improved immunity, and even brain health. Probiotics refer to microorganisms that are beneficial to their host. You might have read the famous quote from Hippocrates that “all disease begins in the gut.” Although this notion has been rejected by the medical community for centuries, current science does suggest there is some truth to it. The human microbiome has been the focus of much research within the medical community, where certain gut-residing microorganisms are linked to better health, and other microorganisms are linked to chronic illness or other disease. Also, it appears that a more diverse probiotic profile correlates with better health. At this time, it is currently unclear what the optimal probiotic profile should be, or whether it should vary from person to person. Generally, the bacteria that are considered healthy include, but are not limited to, bacteria within the genus Lactobacillus and the genus Bifidobacterium. These bacteria are lactic acid producing, which may be linked to their health properties.

We do know that a healthy microbiome is best supported by diets rich in fiber and fermented foods. Research also demonstrates that probiotics are supported by lifestyle factors such as regular exercise, good sleep, and decreased stress. Conversely, unhealthy bacteria tend to thrive in a host that consumes foods high in sugar and processed ingredients. Also, stress and consequent changes in hormone levels can lead to higher populations of unhealthy bacteria, as well as a less diverse microbiome. Interestingly, stress, poor sleep, and diets high in sugar and processed foods have been linked to depression as well.

Since I am a psychiatrist, I am very interested in the gut-brain connection. So how do the gut microbiome and the brain communicate? Certain ideas have been circulating through the literature.

Theory # 1: Neurotransmitter Modulation:

Researchers have found that gut microbiota and the brain communicate via neurotransmitters. Neurotransmitters are chemicals within the body that send signals across nerves and brain cells. Gut microbiota can send signals to the gut nervous system, which sends signals to the vagus nerve, which then transmits signals to the brain.

Also, probiotics can alter the metabolism and availability of serotonin in the body.6 Serotonin is a neurotransmitter that regulates sleep, mood, and appetite. It is a frequent target of antidepressant medications. We do know that boosting serotonin availability in the brain can help decrease depression and anxiety for many people. Serotonin also plays a critical role in the gut. Researchers estimate that over 90% of the body’s serotonin is actually made in the gut, and probiotics support this process. One study at Caltech found that germ free mice (rodents without normal microbiota) had 60% less serotonin circulating in their bodies compared to normal mice (rodents with microbiota).10 Furthermore, restoring a healthy microbiota in germ free mice correlated with an increase in circulating serotonin. 10

In addition, microbiota have also been shown to produce other neuroactive chemicals, such as melatonin, histamine, gamma-aminobutyric acid (GABA), acetylcholamine, and catecholamines.9 These chemicals are often modulated by psychiatric medications and are known to affect cognition, sleep, and mood.

Lastly, short chain fatty acids are produced by certain bacteria, including many probiotics. These act as chemical messengers to the central nervous system, and can also cross the blood brain barrier (the sheath that encapsulates the brain). 6

Theory #2: Immune System Modulation.

Another way the gut microbiome likely communicates with the brain is via the immune system. Microbiota have been shown to influence intestinal permeability, leading to a theory known as leaky gut. Leaky gut occurs when the intestinal wall becomes more porous as a result of toxins, pathogens, stress, and hypersensitivity reactions to foods.5,6 Inflammation in the gut lining leads to less cellular adhesion between gut cells. It is thought that digested food particles, toxins, and pathogens “leak” into the blood stream and cause immune reactions throughout the body. According to leaky gut theory, this leads to a state of chronic inflammation, which could also cause inflammation in the brain. For example, pro-inflammatory molecules have been associated with negative mood and cognitive changes, suggesting an impact on the brain. Some medical practitioners believe that depression and anxiety may be symptoms of leaky gut for some patients. Interestingly, cells within the immune system do have receptors that recognize signals from microbes throughout the body.6 Excessive activation of immune cells by pathogenic bacteria, which may escape a leaky gut, could potentially contribute to chronic inflammation.4

Although the concept of leaky gut is controversial within the medical community, studies do show that intestinal permeability increases in response to acute stress in both animal and human models. We also know that probiotics and their metabolites can help seal the intestinal barrier and tighten the junctions between cells.6 Therefore, treating gut health and supporting beneficial bacteria could in theory decrease chronic inflammation and potentially serve as a treatment target for mood symptoms in certain populations.

Theory #3: Hormonal Modulation.

Stress and microbiota have a bidirectional influence on each other via the hypothalamic-pituitary-adrenal axis (HPA axis). The HPA axis refers to the regions of the brain and body that manage crucial hormones. When we perceive stress, for example, the hypothalamus and pituitary regions of the brain release chemical signals that trigger stress hormones to be released from the adrenal glands. Chronic stress and consequent overactivation of the HPA axis can eventually lead to suboptimal activity of the HPA axis, otherwise known as HPA axis dysregulation. HPA axis dyregulation involves poor stress tolerance, fatigue, brain fog, and has been linked to depression.2 Of note, stress and HPA axis dysregulation negatively alter the microbiome, and have been shown to decrease probiotic populations within the gut.3 At the same time, having a healthy microbiome may help mediate acute stress. Animal studies have shown that rodents without microbiota release abnormally high levels of stress hormones in response to acute stress.8 Furthermore, adding probiotics to germ free rodents helped to normalize the release of stress hormones, thus suggesting a bidirectional influence of gut microbiota and the HPA axis.1

So what does this all mean for you?

At this time, there are no specific recommendations for which specific probiotics best impact brain health. As mentioned previously, however, a more diverse probiotic profile has been linked to better overall health. The lifestyle factors that support a healthy microbiome, such as good sleep, regular exercise, and a whole foods diet, also support general health and mental wellbeing. My recommendation is therefore to engage in lifestyle factors that support a healthy microbiome. As for probiotic supplements, they are generally considered safe unless you have a weakened immune system due to medical illness. Exercise caution when choosing a supplement to minimize the risk of contaminants.

Works Cited:

1. Ait-Belgnaoui, A.; Durand, H.; , Cartier, C.; Chaumaz, G.; Eutamene, H.; Ferrier, L.; Houdeau, E.; Fioramonti, J.; Bueno, L.; Theodorou, V. Prevention of gut leakiness by a probiotic treatment leads to attenuated HPA response to an acute psychological stress in rats. Psychoneuroendocrinology. 2012 Nov; 37(11):1885-95.

2. Barden, N. Implication of the hypothalamic-pituitary-adrenal axis in the physiopathology of depression. J. Psychiatry Neurosci. 2004, 29, 185-193.

3. Foster, J.; Rinaman, L.; Cryan, J. Stress & the gut-brain axis: Regulation by the microbiome. Neurobiol Stress. 2017 Dec; 7: 124–136.

4. Frasca, D.; Blomberg, B. Inflammaging decreases adaptive and innate immune responses in mice and humans. Biogerontology. 2016 Feb;17(1):7-19.

5. Gareau, M.; Silva, M.; Perdue, M. Pathophysiological mechanisms of stress-induced intestinal damage. Curr Mol Med. 2008 Jun; 8(4):274-81.

6. Kelly, J.; Kennedy, J.; PJ; Cryan, J.F.; Dinan, T.; Clarke, G.; Hyland, N. Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front Cell Neurosci. 2015; 9: 392.

7. Noble, E.; Hsu, T.; Kanoski, S. Gut to Brain Dysbiosis: Mechanisms Linking Western Diet Consumption, the Microbiome, and Cognitive Impairment. Front. Behav. Neurosci. 2017, 11,9.

8. Sudo, N.; Chida, Y.; Aiba, Y.; Sonoda, J.; Oyama, N.; Yu, X.N.; Kubo, C.; Koga, Y. Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice. J. Physiol. 2004, 558, 263-275.

9. Wang, Y.; Kasper, L.H. The role of microbiome in central nervous system disorders. Brain Behav Immun. 2014 May;38:1-12.

10.Yano, J.; Yu, K.; Donaldson, G.; Shastri, G.; Liang, Ma P.; Nagler, C.; Ismagilov, R.; Mazmanian, S.; Hsiao, E. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell. Author manuscript; available in PMC 2016 Apr 9.

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