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Gut-brain-immunity: The 2-way street (part 3 of 3)

In this third edition of our three-part series, we’ll explore the relationship between your “second brain” and your immune system. (Go here for the first post, and here for the second.)

Your gut is a very busy place. Of course, right now it’s actively digesting your most recent meal. But along with that, it’s the source of 80-90% of communication with your brain and is home to about 70% of your immune system as gut-associated lymphoid tissue (GALT). Located along the intestinal tract, GALT protects you from pathogens that might make you sick at the same time it allows helpful bacteria to survive.[1]

Approximately 100 trillion micro-organisms (most of them bacteria) live in your gastrointestinal tract,[2] which is the largest barrier between you and the environment.[3] Your microbiome influences the information that travels to your brain via the enteric nervous system, or “second brain.” [4] Communication on this pathway concerns everything from digestion and metabolism to mood, behaviour and immunity.  Now, there’s increasing evidence that the immune system is critical for gut-brain signaling.[5]

Playing telephone

It seems that gut bacteria can influence immune cells in the gut as well as immune cells that reside in the brain. Activating the immune system in the gut and brain plays a role in the creation of new neurons and the ability to create new neural pathways (plasticity) as well as in neuroinflammation and brain injury.5

Roadblock ahead

Obstacles in the two-way communication highway have been identified as possible triggers of neurodevelopmental and psychiatric diseases and disorders, poor cognitive function, and gastrointestinal disorders like inflammatory bowel diseases. And in these situations, gut bacteria imbalance (or dysbiosis) is common.5

Dysbiosis causes intestinal inflammation that can break down the lining of the intestinal wall, which then allows bi-directional flow between the blood stream and the gastrointestinal tract. [6] This means that undigested food, enzymes, bile and gut bacteria may pass through intestinal walls, and go to places they shouldn’t go. Gut permeability or “leaky gut” has been associated with inflammatory bowel disease, colitis and celiac disease.3

Leaky gut is also linked with systemic inflammation, possibly because gut microbes have passed through the intestinal walls.[7] It’s also now clear that intestinal permeability plays a role in autoimmune diseases, including rheumatoid arthritis.[8]

Chronic inflammation, in circular fashion, changes the composition of the microbiome. This can trigger significant changes in behaviour, including the development of cognitive impairment and depression.5

Mood connection

When you’re under stress, your adrenal glands pump out the stress hormone cortisol. If you were in imminent danger, cortisol would be the magic hormone that would sharpen your senses, increase glucose to your bloodstream for the potential flight or fight, and deflect energy from tasks like digestion that wouldn’t be useful in the moment.

In our current world, however, chronic stress seems to be an unfortunate fact of life. As well as being a drain on you emotionally, sustained elevated cortisol levels stimulate unhappy changes in the gut microbiome and an increase in inflammatory compounds associated with anxiety, intestinal movement, and intestinal permeability.[9]

Intestinal movement, of course, refers to the quantity and quality of your bathroom visits. Since cortisol essential tells your body to stop digesting food until the stress goes away – and chronic stress doesn’t go away – it’s easy to see how bowel problems develop.

Other research shows a connection between mood disorders such as anxiety and depression with dysbiosis, leaky gut and low-grade inflammation. What’s not clear is whether the mood disorder caused the dysbiosis or the other way around.7

Clearing the road

The gut microbiome is influenced by the foods we eat, which then alters immune system function. Consuming a varied diet high in fruits, vegetable and fungi provides polysaccharides (fibre) that support a robust microbiome. Bacteria then ferment fibre to produce short-chain fatty acids (SCFA) that provide important health benefits, including helping to temper inflammation. Research also suggests that SCFA play a pivotal role in cross-talk throughout the microbiota-gut-brain axis.[10] 

Find your way with fungi

Functional fungi are a powerful fuel for SCFA production. Because each mushroom leads to the creation of different SCFA with their own health benefits, consider adding a variety to your daily health regimen for all-round support. Reishi has specifically been shown to promote the growth of anti-inflammatory SCFA-producing bacteria. Importantly, lion’s mane not only helps to maintain integrity of the intestinal barrier, but it also helps to increase the diversity and richness of the microbiome.[11]

As additional support, compounds in lion’s mane help to ease stress-induced cells death[12] and may support cellular repair. Studies have shown that hericenones and erinacines in lion’s mane can easily cross the blood-brain barrier. These natural chemicals stimulate the creation of neuron growth factors that maintain and organize neurons and activate the brain.[13]

Your brain may seem like headquarters, but it’s certainly not working alone. For optimal function, mood and health, remember the whole story.

Lisa Petty, PhD thinks a lot about brain health. To learn how to keep your brain clean, enjoy this article  published in Alive magazine.


[1] Ruth, M.R., Field, C.J. The immune modifying effects of amino acids on gut-associated lymphoid tissue. J Animal Sci Biotechnol 4, 27 (2013).

[2] British Medical Journal (2018);361:k2179

[3] Rohr, M., Narasimhulu, C., Rudeski-Rohr, T., & Parthasarathy, S. (2020). Negative Effects of a High-Fat Diet on Intestinal Permeability: A Review, Advances in Nutrition, Volume 11, Issue 1, January 2020, Pages 77–91,

[4] Bastiaanssen, T., Cowan, C., Claesson, M., Dinan, T., & Cryan, J. (2019). Making Sense of … the Microbiome in Psychiatry. The International Journal of Neuropsychopharmacology22(1), 37–52.

[5] Salvo-Romero, E., Stokes, P., & Gareau. M. Microbiota-immune interactions: from gut to brain. LymphoSign Journal7(1): 1-23. 

[6] Talbott, S., Talbott, J., Stephens, B., & Oddou, M. (2020). Modulation of Gut-Brain Axis Improves Microbiome, Metabolism, and Mood. Functional Foods in Health and Disease10(1), 37–.

[7] Fung, T. C. (2020). The microbiota-immune axis as a central mediator of gut-brain communication. Neurobiology of Disease, 136, 104714–104714.

[8]  Guerreiro, C. S., Calado, Â., Sousa, J., & Fonseca, J. E. (2018). Diet, Microbiota, and Gut Permeability-The Unknown Triad in Rheumatoid Arthritis. Frontiers in Medicine, 5, 349–349.

[9] Makris, A. P., Karianaki, M., Tsamis, K. I., & Paschou, S. A. (2020). The role of the gut-brain axis in depression: endocrine, neural, and immune pathways. Hormones (Athens, Greece), 20(1), 1–12.

[10] Silva, Y. P., Bernardi, A., & Frozza, R. L. (2020). The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Frontiers in Endocrinology (Lausanne), 11, 25–25.

[11] Li, M., Yu, L., Zhao, J., Zhang, H., Chen, W., Zhai, Q., & Tian, F. (2021). Role of dietary edible mushrooms in the modulation of gut microbiota. Journal of Functional Foods, 83, 104538–.

[12] Sabaratnam, V., Kah-Hui, W., Naidu, M., & Rosie David, P. (2013). Neuronal health - can culinary and medicinal mushrooms help?. Journal of traditional and complementary medicine3(1), 62–68.

[13] Ryu, S. H., Hong, S. M., Khan, Z., Lee, S. K., Vishwanath, M., Turk, A., Yeon, S. W., Jo, Y. H., Lee, D. H., Lee, J. K., Hwang, B. Y., Jung, J.-K., Kim, S. Y., & Lee, M. K. (2021). Neurotrophic isoindolinones from the fruiting bodies of Hericium erinaceus. Bioorganic & Medicinal Chemistry Letters, 31, 127714–127714.