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  • Writer's pictureKale Diagnostics Research

Your Second Brain: The Gut

Updated: Oct 10, 2022

As you toss and turn from another night of restlessness, you reflect on your health over the years and wonder, how did I get here? Throughout your life you’ve probably never made the connection, at no fault of your own, it seemed only a minor inconvenience at the time: a parent’s divorce, extended antibiotics for acne, hormonal contraceptives, constipation, antacids, anti-anxiety medications, excessive bloating, hair loss, weight gain, irregular periods, fatigue and struggling to conceive. Could there be a common denominator in all of this?

The research is fairly new, only emerging over the last 20 years or so, and probably in the area you may have least suspected to hold so much power: your gut, more formally known as your gastrointestinal tract.

The gut microbiome is the living environment in your gastrointestinal tract that hosts trillions of bacteria responsible for digestion, absorption, regulation of hormones, immune function and as research has recently revealed, involvement in chronic diseases and mental health [1]. Everything you consume or have consumed in your life has passed through your microbiome impacting the quality and quantity of the bacteria present. External and genetic influences can create more ‘bad’ bacteria than ‘good’ bacteria in what is referred to as a dysbiosis of the gut [2,3]. Numerous studies have found significant dysbiosis of the gut in individuals with PCOS [3], endometriosis [1], Hashimoto’s Thyroiditis [2], hypothyroidism [2], anxiety [4,5], depression [4,5] and metabolic syndromes [1,5]. The undetermined factor is whether these individuals were born with certain ‘bad’ strands of bacteria which caused a disease or whether the disease led to poor quality of the gut bacteria. Nevertheless, the research proves the imperative role of the gut in the overall functioning of the human body which is why researchers often refer to the gut as the ‘Second Brain’. Let’s take a deeper dive to see how your gut health can regulate hormones and homeostasis which can prevent or cause these neuro-immuno-endocrine conditions.


The walls of your gut lining are described as selectively permeable, meaning it is selective as to what is allowed to cross through the barrier and enter into your bloodstream [3]. Imagine a coffee filter with minuscule holes only suited for the essentials you want to pass through, water and caffeine, while holding back the bitter coffee grounds; your gut wall functions in a similar fashion. It allows only the essential nutrients and water to pass through while preventing waste products, pathogens or diseases from being able to cross the barrier [3,6]. You wouldn’t reuse a coffee filter multiple times because it would get weak, clogged with old coffee grounds and eventually larger holes will penetrate the filter from the sogginess leaving you with bitter grounds in your cup. Similarly, without care and nourishment to your gut lining the structure of the wall can become weakened thereby increasing the permeability allowing particles to enter your bloodstream which should not be there. Your body views these unwanted particles as foreign invaders and in turn mounts an immune response leading to inflammation, insulin resistance and stress (more on stress below) [3,6]. This is what is theorized as ‘Leaky Gut’ Syndrome: the increased permeability of the gut lining to foreign, unwanted molecules that cause your body to enter a state of inflammation.

So, what makes a gut ‘leaky’?

The bacteria in your gut are the primary determinants of increased intestinal permeability. Fiber from carbohydrates we consume (known as prebiotics) are fuel for the bacteria. After digestion and metabolism of carbohydrates, the ‘good’ bacteria (probiotics) produce products essential for gut functioning, signaling and the gut wall barrier. These end products are known as postbiotics. The presence of ‘bad’ bacteria, or dysbiosis, interferes with the ‘good’ bacteria’s ability to consume the fiber sources and can therefore affect the type and amount of postbiotics produced. In an ideal scenario, the majority of postbiotics produced are called short-chain fatty acids (SCFA’s) which are an integral part of the intestinal wall barrier as well as a contributor to a protective mucous layer in the lining, a role in immune function, neuroinflammation and hormone production [7,8]. Figure 1 shows the mechanism by which our food is converted into SCFA’s and its effect on multiple systems throughout the body. The bacteria, or microbiota, present in your gut which determine the pathway of SCFA’s produced have been developing, growing and multiplying since before you were even born so having a ‘leaky gut’ is not a result of the dairy you consumed last week, it is years of stressors and genetic factors that led you to where you are today [1]. Some studies suggest around 40-60% of your microbiome was inherited from your mother’s gut environment while the remainder continues to be influenced throughout your life by factors such as whether you were born vaginally or by cesarean section, breastfed or formula fed, your diet as a toddler, stressors throughout life such as a parent’s divorce, extended antibiotic usage (which destroys ‘good’ bacteria), exercise habits, sleeping habits and, of course, dietary choices [1,7]. Short-chain fatty acids aren’t the only player in intestinal wall integrity, there is another important family of bacteria that has a significant role in gut health known as your Estrobolome.


Adrenal Gland: Two glands located on top of the kidneys that produce hormones such as Testosterone and Cortisol that help regulate blood pressure, immune system, metabolism and response to stress

Autonomic Nervous System: A system in your body that regulates involuntary processes such as heart rate, blood pressure, respiration, digestion and sexual arousal

Dysbiosis: A state of being of the presence of more ‘bad’ bacteria than ‘good’ bacteria

Gut Microbiome: The environment of the gut that hosts trillions of bacteria responsible for digestion, absorption of nutrients and immune function

Homeostasis: A state of equilibrium and balance in the body between physiological processes

HPA Axis: The hypothalamic-pituitary-adrenal axis is the linkage of these three areas of the body that secrete hormones to provide direct communication with each other whether to stimulate or suppress

Hypothalamus: A region of the brain responsible for maintaining homeostasis by temperature regulation, appetite control, energy requirements, memory and stress

Permeability: The state or quality of the membrane that allows liquids or gasses to pass through it

Pituitary:A gland located in the brain responsible for regulation of hormone secretions such as Thyroid Stimulating Hormone, Luteinizing Hormone, Follicle Stimulating Hormone and Adrenocorticotropic Hormone which stimulates the Adrenal Gland

Postbiotics: The end product of prebiotics and probiotics; created by digestion and contribute to gut health

Prebiotics: Compounds in food, mostly fiber sources from carbohydrates, that provide the gut microbiome with fuel for growth and development

Probiotics: Live microorganisms in the gut that can improve or restore gut flora: ‘good’ bacteria

Short-chain fatty acids: Postbiotics that send messaging to other areas of the body involved in hormone production and play a vital role in intestinal wall protection and integrity

Vagus Nerve: The main nerve in the parasympathetic nervous system that controls involuntary functions such as digestion, heart rate and immune system


1. Liu S, An Y, Cao B, Sun R, Ke J, Zhao D. The composition of gut microbiota in patients bearing Hashimoto’s thyroiditis with Euthyroidism and hypothyroidism. International Journal of Endocrinology. 2020;2020:1-9. doi:10.1155/2020/5036959

2. Xu F, Fu Y, Sun T-yu, et al. The interplay between host genetics and the gut microbiome reveals common and distinct microbiome features for complex human diseases. Microbiome. 2020;8(1). doi:10.1186/s40168-020-00923-9

3. Lingaiah S, Arffman RK, Morin-Papunen L, Tapanainen JS, Piltonen T. Markers of gastrointestinal permeability and dysbiosis in premenopausal women with PCOS: A case–control study. BMJ Open. 2021;11(7). doi:10.1136/bmjopen-2020-045324

4. Breit S, Kupferberg A, Rogler G, Hasler G. Vagus nerve as modulator of the brain–gut axis in psychiatric and inflammatory disorders. Frontiers in Psychiatry. 2018;9. doi:10.3389/fpsyt.2018.00044

5. Groot H, Van De Vegte YJ, Verweij N, Lipsic E, Karper JC, Van Der Harst P. Human genetic determinants of the gut microbiome and their associations with health and disease: A phenome-wide association study. European Heart Journal. 2020;41(Supplement_2). doi:10.1093/ehjci/ehaa946.3642

6. Nie X, Xie R, Tuo B. Effects of estrogen on the gastrointestinal tract. Digestive Diseases and Sciences. 2018;63(3):583-596. doi:10.1007/s10620-018-4939-1

7. Silva YP, Bernardi A, Frozza RL. The role of short-chain fatty acids from gut microbiota in gut-brain communication. Frontiers in Endocrinology. 2020;11. doi:10.3389/fendo.2020.00025

8. Baker JM, Al-Nakkash L, Herbst-Kralovetz MM. Estrogen–gut microbiome axis: Physiological and clinical implications. Maturitas. 2017;103:45-53. doi:10.1016/j.maturitas.2017.06.025

9. Jiang Y, Greenwood-Van Meerveld B, Johnson AC, Travagli RA. Role of estrogen and stress on the brain-gut axis. American Journal of Physiology-Gastrointestinal and Liver Physiology. 2019;317(2). doi:10.1152/ajpgi.00144.2019

10. Marcondes Ávila PR, Fiorot M, Michels M, et al. Effects of microbiota transplantation and the role of the vagus nerve in gut–brain axis in animals subjected to chronic mild stress. Journal of Affective Disorders. 2020;277:410-416. doi:10.1016/j.jad.2020.08.013

11. Anatomy and function of the hypothalamus. IntechOpen. Accessed August 14, 2022.

12. Rosin S, Xia K, Azcarate-Peril MA, et al. A preliminary study of gut microbiome variation and Hpa Axis reactivity in healthy infants. Psychoneuroendocrinology. 2021;124:105046. doi:10.1016/j.psyneuen.2020.105046

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