A few decades ago, our understanding of the gut only represented a long tube, secreting a variety of enzymes with 2 openings. One to feed, the other to get rid of waste products through defecation. Since then, science has gone a long way, and a complex universe called the microbiome has now been discovered.
The microbiome represents the trillions of bacteria, viruses, fungi, protozoa and other microscopic organisms colonising everything from our mouth to our rectum with the largest density living in colon (the final part of the digestive tract). The density here is so thick that it would take up to 20 planet Earths to match the population of bacteria living on 1 square centimetre of the large intestine.
The microbiome has now become a new target for mental & cognitive health therapies. It has been found that people with conditions such as dementia, Alzheimer’s, depression, panic attacks, schizophrenia, autism and bipolar disorder often have significant disruptions to their microbiome and that a restoration of healthy balance has, in some studies, produced significant benefits for these people. This suggests that the effects of microbiome are not only localised to the digestion (e.g. helping to digest fibre) but have far and wide effects on other systems including cardiovascular health, immune system, metabolism & blood sugar control, weight management, energy production, mental health, motivation, a feeling of happiness and fulfilment, skin health, detoxification, bone health, sex health & fertility.
In this article, we will start to unravel this mysterious connection and what are some of the hidden forces in play. Towards the end, you will understand why you need to protect this delicate balance like your baby and do absolutely everything within your power to protect it as such. In the second part, we will look at how to do just that.
WHAT IS THE GUT-BRAIN CONNECTION?
The human body never works in isolation. Nothing inside of the body is an island and everything communicates with everything else all the time, which is why it is not a surprise that the brain and the gut are connected through an important route called the gut-brain axis. This is a complex pathway of hormones, neurotransmitters, enzymes and a variety of signalling chemicals. The gut-brain axis works on 2 levels: top-down and bottom-up
TOP-DOWN COMMUNICATION
The top-down communication starts at the level of the brain and is administered through 3 systems
1. The Enteric Nervous System (ENS) – this is the nervous system of the gut a vast maze of neurons that are directly connected to the brain through the largest nerve in the body called the Vagus Nerve. Ever felt butterflies in your stomach when you were stressed? This is why. The ENS works by relaying chemical signals from the gut through the nervous system directly into the executive parts of the brain. It regulates the most crucial factors related to survival in the gut, such as PH, amino acid balance, glucose profile, blood flow into the gut walls, absorption, regulation of digestive secretions & enzymes and much more. Basically, this is the brain of your digestive system.
2. The Autonomic Nervous System (ANS) – The enteric nervous system is one of the many branches of the autonomic nervous system. The ANS regulates stress response across the whole body. When needed, it can override the function of ENS (e.g. when survival is threatened). It is responsible for the production of stress hormones and for deciding whether the body is in a “peaceful state” (rest & digest) or on an “alert state “( fight or flight).
3. The Central Nervous System (CNS) – This is the highest executive levels of the nervous system. It regulates both the autonomic and the enteric nervous system branches. The main 2 elements are the brain & the spinal cord. CNS regulates everything that happens in the body, including involuntary functions such as heartbeat, unconscious breathing, blood flow, muscular function, bone density, organ function, detoxification. The CNS is the CEO of the human body.
BOTTOM-UP COMMUNICATION
The walls of the intestines are producing hundreds of different molecules that have a direct effect on the brain & the rest of the body. These chemicals are produced by:
1. the digestive system itself, for example, by the cells embedded in the wall of intestines called endothelial cells
2. by the microorganisms that create our microbiome
3. by the part of the immune system embedded inside the human gut called Gut-Associated Lymphoid Tissue & Payer’s Patches (for simplicity referred to as Gut Immunity)
HOW DOES THE MICROBIOME IMPACT THE BRAIN?
While the top-down communication is fairly well researched and established the bottom up (microbiome to brain) is still under a lot of research simply due to its endless complexity and hundreds of different species all of which do different things and communicate with our body in a different ways. Some of the ways through which microbiome may establish communication with the brain (and also how this can go wrong) are described below.
1. NEUROTRANSMITTERS
You’ve probably come across some of these terms before. Adrenaline, noradrenaline, serotonin, dopamine, GABA, glutamate, acetylcholine. These are chemical messengers. They establish communication through the nervous system to the rest of the body (including digestion). Historically it used to be thought that these are only made in the brain and few specific organs such as adrenal glands, but it has now been discovered that all these signalling molecules are also made in the gut and in much larger quantities. And while they cannot enter the brain directly due to the blood-brain barrier (a defensive wall protecting the brain from toxins), they can dock into a variety of receptors in the gut and send signals to the brain through the Enteric Nervous System. For example, having an abundance of serotonin and serotonin-making bacteria in the gut keeps the brain happy. It sends signals through the bottom-up pathways saying, “we are healthy & happy down here” nothing to worry about. Having an abundance of dopamine-making species improves motivation and drive. Noradrenaline-producing species improve general vigour & that sort of “wild drive” to get out there and change the world. Other species making a neurotransmitter called GABA (gamma-aminobutyric acid) help us feel more grounded and at peace with the world. Of course, we need a balance of all. Enough GABA to prevent going into overdrive and getting panic attacks but at the same time having enough serotonin and noradrenaline to prevent slipping into depression and chronic fatigue.
2. SHORT-CHAIN FATTY ACIDS
The second piece of the puzzle are a so-called Short-Chain Fatty Acids (SCFA). The 4 dominant ones are acetate, propionate, butyrate and valerate. When our beneficial bacteria in the gut come in contact with fibre from the food (prebiotics), they start consuming it, and in exchange, produce SCFAs. A tiny portion of SCFAs produced in the gut can make their way to the brain, where they exert powerful effects, including:
reduction of brain inflammation (brain inflammation is common in depression and dementia)
support of BDNF (see previous blog articles for more info on this)
improved learning, attention & memory
improved overall brain performance & creativity
improved sleep (lack of sleep is a severe disruptor of mental health)
support the integrity of the blood-brain barrier
promote the production of growth hormone (growth hormone has an impact on mental health)
promote the function of microglia (immune cells in the brain essential in the process of neuroplasticity and brain protection from inflammation, free radicals and toxins)
promote the development of a baby’s brain in the utero
3. CHRONIC INFLAMMATION
Inflammation is a natural response of the human body to an external offence, including mechanical injury, pathogenic invasion, toxins, heavy metals but also food can stimulate mild inflammation. We need a certain amount of inflammation, and there is a small level of it present somewhere in the body all the time. What is problematic, however, is chronic inflammation. The type of inflammation that is medium-to-high for years and years and remains unaddressed. Chronic inflammation in the body has a negative effect on the central nervous system. It has been found that chronic inflammation in conditions such as obesity, diabetes, inflammatory bowel disease (IBD) has a direct effect on the brain and cognitive health. Chronic inflammation is in the middle of all neurodegenerative conditions such as Alzheimer’s, Parkinson’s, Multiple Sclerosis, Lyme’s disease but also oncologic disease of the brain. Chronic inflammation in the body leads to 2 phenomena:
Increase permeability of the gut (“leaky gut” syndrome) – we will talk about this in the future
Increased permeability of the blood-brain barrier – I will also explore this in the future; also see point 5.
Both of the above are risk factors for serious health consequences unless addressed. The latter allows for the migration of toxins, bacteria and heavy metals in the brain, which can cause extremely serious health consequences.
In addition, chronic inflammation in the gut can damage even destroy the communication sites that are used to send signals to the brain. This could mean that the brain no longer receives all signals about the situation in the gut but it could also mean the development of constipation and severe digestive problems since the brain is also responsible for gut motility and gut secretions (enzymes, bile, acids etc.).
Certain types of gut bacteria also create regulatory molecules responsible for shutting down inflammation. Should we lose the diversity of these by losing the healthy microbial balance, the body will struggle to stop the inflammation once it has run its course.
4. CHRONIC STRESS
Chronic stress is extremely detrimental to the gut-brain axis.
First of all, it reduces the diversity of different colonies of beneficial bacteria in the microbiome. It may increase the permeability of the intestinal walls (also known as leaky gut), which is a toxic state and a suspected cause of many autoimmune conditions. Chronic stress also raises levels of chronic inflammation in the body (see chapter above). It leads to making poor food choices (emotional crutches such as high salt, high fat, high sugar foods as well as alcohol) which then further damages the microbiome-brain connection.
5. BLOOD BRAIN BARRIER (BBB) INTEGRITY
BBB is a complex system of different proteins that protect the human brain from pathogens, toxins, metals and metabolic waste products. While it used to be thought that it is a rigid impenetrable structure, we now know that BBB is a highly dynamic system. Certain molecules such as short-chain fatty acids (see above) support its structure and density while other things may temporary open it, causing an influx of potentially harmful molecules that should not be in the brain. Some of these BBB-openers are chronic inflammation, dysbiosis (imbalance of microbiome species), pathogenic bacteria from the gut.
6. VITAMIN SYNTHESIS
Certain strains of gut species (For example: Escherichia coli, Klebsiella pneumoniae, Propionibacterium, Eubacterium, Bacillus Subtilis, Bifidobacterium, Lactococcus Lactis, Streptococcus Thermophilus, Lactobacillus Reuteri and Propionibacterium Freudenreichii) can synthesise vitamins: K, B9 & B12 all of which are essential cofactors in brain and central nervous system health.
For example, vitamin B12 is responsible for the production & protection of the central nervous system coating called the myelin sheath. Damage to myelin sheath is common in 2 conditions: multiple sclerosis & vitamin B12 deficiency. Both can be life-threatening if unmanaged—more the reason to protect your microbiome.
Vitamin B9 (Folate) is responsible for neuronal development in child and adults. it also plays a role in a complex biochemical process called methylation, which helps clear out homocysteine, a molecule that can lead to early stroke or atherosclerosis if left unchecked and if not cleared effectively.
Low levels of Vitamin K may contribute to systemic coagulation and to diseases such as Alzheimer’s, Parkinson’s or stroke due to formation of clots.
These are just a few of many potential interactions between the gut & microbiome with the brain. Many of the communication systems have not been identified yet, and some of them are only understood very vaguely.
KEY SUMMARY POINTS
The gut-brain microbiome is a complex bidirectional communication system that establishes the exchange of information from brain to the gut and from gut to the brain and the enteric nervous system.
The top-down communication happens through the central nervous system, the autonomic nervous system and the
This communication is established through: neurotransmitters, short-chain fatty acids, certain hormones, blood brain barrier, different gut metabolites, gut bacteria and certain vitamins
The gut-brain axis may be disrupted by: chronic stress, chronic inflammation, damage to the microbiome balance and damage to the blood brain barrier
IN NEXT PART WE WILL EXPLORE:
How to optimise the health & balance of your microbiota?
What are probiotics and prebiotics? What’s the difference? Do you need them?
How can you harness the maximum potential of limited budget to eat the highest quality foods on the planet and to support your microbiome?
What harms your microbiome and what activities you need to avoid?
WANT TO LEARN MORE ABOUT MEN'S HEALTH & WELLBEING?
Check out my free e-book on men's health. Learn about how to optimise your nutrition, sleep, brain performance, testosterone, workout and much more.
FOLLOW ANDRO HEALTH
Make sure to stay on the top of latest updates by following Andro Health Nutrition on Facebook and/or Instagram for regular updates in health & nutrition to maximise your health potential.
SOURCES
Banks, W.A. (2008). ‘The Blood-Brain Barrier: Connecting to the Gut and the Brain’, HHS Public Access, 149, (1-3), pp. 11-14
Banskota, S. Khan, W.I. Ghia, J.E. (2018). ‘Serotonin in the gut: Blessing or a curse’, Biochimie, 161, pp.56-64.
Benaki, C. Martin-Gallausiaux, C. Trezzi, J.P. et al. (2020). ‘The microbiome-gut brain axis in acutee and chronic brain diseases’, Current Opinion in Neurobiology, 61, pp.1-9.
Ding, J.H. Jin, Z. Yang, X. et al. (2020). ‘Role of the gut microbiota via the gut-liver-brain axis in digestive diseases’, World Journal of Gastroenterology, 26 (40), pp.6141-62.
Galland, L. (2014). ‘The Gut Microbiome and the Brain’, ‘Journal of Medicinal Food’,17(12), pp.1261-1272.
Jang, S.H. Woo, Y.S. Lee, S.Y. et al. (2020). ‘The Brain-Gut-Microbiome Axis in Psychiatry’, International Journal of Molecular Sciences, 21 (19), 7122.
Liang, S. Wu, X. Hu, X. et al. (2018). ‘Recoignizing Depression from the Microbiota-Gut-Brain Axis’, International Journal of Molecular Sciences, 19 (6), pp.1592.
Madison, A. & Kiecolt-Glaser, J.K. (2019). ‘Stress, depression, diet, and the gut microbiota: human– bacteria interactions at the core of psychoneuroimmunology and nutrition’, Current Opinion in Behavioral Sciences, 28, pp.105-110
Parker, A. Fonesca, S. Carding, S.R. (2020). ‘Gut microbes and metabolites as modulators of blood-brain barrier integrity and brain health’, Gut Microbes, 11 (2), pp.135-157.
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, 11 (25).
Winter, G. Hart, R.A. Charlesworth, R. (2018). ‘Gut microbiome and depression: What we know and what we need to know’, Reviews in Neurosciences, 29 (6), pp.629-643.
Zhu, S. Jiang, Y. Xu, K. et al. (2020). ‘The progress of gut microbiome research related to brain disorders’, Journal of Neuroinflammation, 17 (1), pp.25.