The Gut-Brain Axis: Driver of Health and Disease

The brain and the gut “talk” to each other, influencing various aspects of your health.

The brain controls every aspect of our body, regulating the function of cells and organs from the head to the tip of our toes and influencing all aspects of our health. An important connection, commonly known as the gut-brain axis, involves a bi-directional communication pathway that exists between the gastrointestinal tract (GIT) and the brain. The Gut-Brain axis is possible thanks to the interaction of various other parts of the body, including the vagus nerve, the sympathetic nervous system, the endocrine and immune systems, as well as the gut microbiota^1-4.

The Gut-brain connection

The human nervous system is divided in the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS is composed of the brain and the spinal cord, whereas the PNS include all the billions of neurons and the nerves that are distributed throughout the body. An important component of the PNS is the Autonomic nervous system (ANS), which controls all of our involuntary body actions, including our heart rate, digestion, respiration, urination, sexual arousal, and others.  The Enteric nervous system (ENS) is one of three divisions of the ANS, the other two being the Sympathetic and the Parasympathetic systems.

The ENS is the nervous system of the gut: it contains as many as 600 million neurons distributed across the gastrointestinal tract, from the oesophagus to the anus³. These millions of neurons integrate information about the health and status of the gastrointestinal tract and direct important functions, like intestinal movement, fluid exchange between the gut and its lumen, inflammatory responses and local blood flow^5-6.

The ENS also has extensive two-way connections with the Central nervous system. Together, these two systems control the digestive system to meet the physiological demands of the body.

How is our brain connected to the gut?

Our brain is connected to the gastrointestinal tract (the gut) through nerves and biochemicals, including:

• The Enteric nervous system and the Vagus nerve (the main component of the Parasympathetic system), which represents the two main neuronal mechanisms connecting the gut and the brain⁷.
• Biochemical molecules, like neurotransmitters, which allow for the transmission of messages between the brain and the gut⁸.
  • Neurotransmitters function as chemical messengers between neurons and include molecules like serotonin, histamine dopamine.

How is the gut-brain axis connected to health?

Gut dysfunction has been linked to various diseases, including immune and metabolic disorders, heart disease, neurological conditions and gut-related problems.

Some of health conditions linked to the gut-brain axis include:

• Conditions linked to gut dysbiosis – The human gut is home to billions of bacteria, archaea, fungi, and viruses, collectively known as the gut microbiota. They form a vast community of microbes interacting among themselves and with the cells in your gut. Most of these microorganisms are found in the large intestine, and research has revealed amazing links with various aspects of human health^9-10. For example,
  • One of the best studied mechanisms linking gut microbiome and health involve the multiple biochemicals these microorganisms produce, known as metabolites, which include short chain fatty acids, tryptophan metabolites and retinoic acid¹¹. Alterations to the optimal levels of these metabolites can result in a weakened immune system, making it more propense to diseases. Original table and accompanying references found here

• • Alterations to the optimal composition of the gut microbiota has been associated with multiple pathologies, including neurological conditions (e.g. Alzheimer, depression and Parkinson’s disease), atherosclerosis, bone health, hypertension, heart disease, chronic kidney disease, obesity, and type 2 diabetes mellitus, and immune-related disorders, among other conditions^8,12-13.

• Gut dysfunction and health – beyond gut dysbiosis there are other pathologies of the gut that are linked to disease. One of the most important gut-related pathologies is defective intestinal permeability. One of the key functions of the GIT is to serve as a protective barrier that prevents pathogens to enter the bloodstream. This barrier also allows for the selective entry of nutrients needed by the body¹⁴.
  • Alterations to intestinal permeability can lead to impaired intestinal function and has been associated with conditions like inflammatory bowel disease, obesity, and metabolic disorders.
  • An important factor affecting intestinal permeability is pathogen infections. For example, infection by Helicobacter pylori can affect the function of cells responsible for intestinal permeability. This could potentially lead to an increased chance of developing conditions like peptic ulcer disease and gastric cancer¹⁵.

 Our health is affected by multiple factors, including genetics, diet and lifestyle options like exercise, and sleep patterns. Optimising the function of the brain-gut axis is an important way to avoid disease, improve the function of multiple systems in our body and improve our health.

References

1. Carabotti M, Scirocco A, Maselli MA, Severi C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Annals of gastroenterology: quarterly publication of the Hellenic Society of Gastroenterology. 2015 Apr;28(2):203. Read it!
2. Bonaz B, Bazin T, Pellissier S. The vagus nerve at the interface of the microbiota-gut-brain axis. Frontiers in neuroscience. 2018 Feb 7;12:49. Read it!
3. Furness JB, Callaghan BP, Rivera LR, Cho HJ. The enteric nervous system and gastrointestinal innervation: integrated local and central control. InMicrobial endocrinology: The microbiota-gut-brain axis in health and disease 2014 (pp. 39-71). Springer, New York, NY. Read it!
4. Dinan TG, Cryan JF. Gut–brain axis in 2016: Brain–gut–microbiota axis—mood, metabolism and behaviour. Nature Reviews Gastroenterology & Hepatology. 2017 Jan 5;14(2):69. Read it!
5. Gershon MD. Nerves, reflexes, and the enteric nervous system: pathogenesis of the irritable bowel syndrome. Journal of clinical gastroenterology. 2005 May 1;39(5):S184-93. Read it!
6. Furness JB. The enteric nervous system. Blackwell Pub.; 2006 Jan 1. Read it!
7. 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 Mar 13;9:44. Read it!
8. Mittal R, Debs LH, Patel AP, Nguyen D, Patel K, O’Connor G, Grati MH, Mittal J, Yan D, Eshraghi AA, Deo SK. Neurotransmitters: The critical modulators regulating gut–brain axis. Journal of cellular physiology. 2017 Sep;232(9):2359-72. Read it!
9. Rajilić‐Stojanović M, Smidt H, De Vos WM. Diversity of the human gastrointestinal tract microbiota revisited. Environmental microbiology. 2007 Sep;9(9):2125-36. Read it!
10. Zoetendal EG, Rajilić-Stojanović M, De Vos WM. High-throughput diversity and functionality analysis of the gastrointestinal tract microbiota. Gut. 2008 Nov 1;57(11):1605-15. Read it!
11. Rooks MG, Garrett WS. Gut microbiota, metabolites and host immunity. Nature Reviews Immunology. 2016 Jun;16(6):341-52. Read it!
12. Boulangé CL, Neves AL, Chilloux J, Nicholson JK, Dumas ME. Impact of the gut microbiota on inflammation, obesity, and metabolic disease. Genome medicine. 2016 Dec;8(1):1-2. Read it!
13. Foster JA, Neufeld KA. Gut–brain axis: how the microbiome influences anxiety and depression. Trends in neurosciences. 2013 May 1;36(5):305-12. Read it!
14. Bischoff SC, Barbara G, Buurman W, Ockhuizen T, Schulzke JD, Serino M, Tilg H, Watson A, Wells JM. Intestinal permeability–a new target for disease prevention and therapy. BMC gastroenterology. 2014 Dec 1;14(1):189. Read it!
15. Amieva MR, Vogelmann R, Covacci A, Tompkins LS, Nelson WJ, Falkow S. Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA. science. 2003 May 30;300(5624):1430-4. Read it!