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Gut-Brain-Immune Axis: An Introduction

Introduction to the gut-brain-immune axis

The human’s gut consists of a certain composition of beneficial microorganisms that is unique to every individual, which is also known as the gut microbiota. On top of the usual gastrointestinal processes such as digestion and absorption, this composition of microorganisms has also been found to play a significant role in several other functions and diseases that are otherwise seemingly unrelated to the gut. Why and how is this gut-brain-immune axis possible?

Read on to find out more about this fascinating interaction between the gastrointestinal system, central nervous system, and the immune system.

Understanding the gut microbiota and its functions

Before we try to understand this complex interaction of the gut-brain-immune axis, let’s first understand what the gut microbiota is, what it does, and what happens when there is a change in this composition.

The gut microbiota consists of different types of microorganisms, ranging from bacteria, fungi, and viruses [1]. This composition is unique to everyone due to the impact from multiple factors including environmental and lifestyle factors [2]. One of the functions of the gut microbiota is to breakdown indigestible substrates like dietary fibers and intestinal mucus, producing short-chain fatty acids (SCFAs) and gases in the large intestine. These SCFAs are associated with several health benefits, including metabolism, homeostasis, controlling gut hormones, and lower rates of obesity[3].

Other gastrointestinal functions of the gut microbiota include the synthesis and absorption of vitamins and nutrients such as vitamin K and vitamin B, as well as maintain the integrity and structure of the gut barrier[4].

A change in the composition of the gut microbiota can happen due to several factors, including drugs (e.g., excessive use of antibiotics), toxins and pathogens[5]. This is also called ‘dysbiosis’, and this affects the permeability of the gut’s barriers.

How the gut microbiota affects the other body systems

Other than the effects the gut microbiota have on the gastrointestinal system, it also works and communicates with other systems such as the immune system and the central nervous system (including the brain).

The immune system is especially connected with our gastrointestinal system, as evidenced from the fact that more than 70% of immune cells are found in the gut[6]. The interactions between the gut microbiota and the immune system are thought to be via the SCFAs that are produced as by-products of the indigestible substrates (e.g., dietary fibers)[7]. These SCFAs are involved in the homeostasis of immune cells through several receptors[8], and act as key metabolites for the functioning of the intestinal surface layer. The intestinal surface layer, where the gut microbiota resides, also acts as a first line of defense for the body against incoming pathogens.

The gut microbiota also has a bidirectional communication with the central nervous system (CNS), including the brain. This interaction is often coined as the ‘gut-brain axis’. For one, the gut is physically connected to the nervous system and the brain via the vagus nerve. It is thought that the interaction between the gut and brain also otherwise happens via several pathways [9]:

Neurological

SCFAs such as butyrate (produced by the gut microbiota by breaking down dietary fiber) also affect CNS functions such as the formation of the blood brain barrier (BBB) [10], which shields the brain from toxic substances and filters chemicals to the blood [11].

Endocrinological

Chemicals that can affect brain cell physiology (i.e., neurotransmitters) are produced by some of the species within the gut microbiota[2]. One such neurotransmitter is serotonin, which also plays a part in affecting an individual’s mood.

Immunological

Gut microbiota also affects mucosal immune activation. An increase in inflammation was seen in studies involving mice after they were treated with oral antibiotics [9]. It is thought that this activation may be due to enzymes such as proteases [9].

Dysbiosis (i.e., alteration in the gut microbiota) is also associated with many hosts diseases, including diseases related and not related to the gastrointestinal system. Some of these includes [5]:

What can we do?

The role of supplementation to improve the gut health is not only important for the gut’s health but is also paramount for the development of other crucial systems such as the immune system and nervous systems. As mentioned in this article, dysbiosis has also been associated with several diseases, including even autism via the gut-brain axis [13]. Hence, developing the gut microbiota is an important thing to do that should not be missed out.

Consumption of dietary fiber and prebiotics promotes for diverse microbiota growth [14]. Other than promoting for microbial growth, dietary fibers are also important in providing substrates for the gut microbiota to form SCFAs, which have been found to be beneficial in multiple functions and developments as described above in this article.

Another consideration may be the excessive use of antibiotics in children, which has been associated with dysbiosis as well. Antibiotics use has also been linked with several diseases such as asthma and juvenile arthritis [15]. Parents should also not request for antibiotics use excessively and unnecessarily for their children to prevent possible dysbiosis as well.

Conclusion

The benefits of a healthy gut extend beyond the gastrointestinal system. Healthy gut microbiota has also been thought to have beneficial effects on the health of other systems, particularly the immune and nervous systems. Consider better nutrition and supplementations to improve our gut health, which have beneficial effects extending beyond that and into the nervous and immune systems.

References

  1. Thursby E, Juge N. Introduction to the human gut microbiota. Biochem J. 2017;474(11):1823-1836. Available on: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433529/
  2. Rutsch A, Kantsjö JB., Ronchi F. The Gut-Brain Axis: How Microbiota and Host Inflammasome Influence Brain Physiology and Pathology. Immunol. 2020;11. Available on: https://www.frontiersin.org/articles/10.3389/fimmu.2020.604179/full
  3. Valdes A M, Walter J, Segal E, Spector T D. Role of the gut microbiota in nutrition and health. 2018; 361:k2179. Available on: https://www.bmj.com/content/361/bmj.k2179
  4. Jandhyala SM, Talukdar R, Subramanyam C, et al. Role of the normal gut microbiota. World J Gastroenterol. 2015;21(29):8787-8803. Available on: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4528021/
  5. Carding S, Verbeke K, Vipond DT, et al. Dysbiosis of the gut microbiota in disease. Microb Ecol Health Dis. 2015;26:26191. Available on: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4315779/
  6. UCLA Health. If you want to boost immunity, look to the gut. 2021 March. Available on: https://connect.uclahealth.org/2021/03/19/want-to-boost-immunity-look-to-the-gut/
  7. Yoo JY, Groer M, Dutra SVO, et al. Gut Microbiota and Immune System Interactions [published correction appears in Microorganisms. 2020 Dec 21;8(12):]. Microorganisms. 2020;8(10):1587. Available on: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7602490/
  8. Rooks MG, Garrett WS. Gut microbiota, metabolites and host immunity. Nat Rev Immunol. 2016;16(6):341-352. Available on: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541232/
  9. Carabotti M, Scirocco A, Maselli MA, Severi C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol. 2015;28(2):203-209. Available on: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367209/
  10. Bourassa MW, Alim I, Bultman SJ, Ratan RR. Butyrate, neuroepigenetics and the gut microbiome: Can a high fiber diet improve brain health?. Neurosci Lett. 2016;625:56-63. Available on: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4903954/
  11. Persidsky Y, Ramirez SH, Haorah J, Kanmogne GD. Blood-brain barrier: structural components and function under physiologic and pathologic conditions. J Neuroimmune Pharmacol. 2006 Sep;1(3):223-36. Available on: https://link.springer.com/article/10.1007/s11481-006-9025-3
  12. Collins J, Borojevic R, Verdu EF, et al. Intestinal microbiota influence the early postnatal development of the enteric nervous system. Neurogastroenterol Motil. 2014 Jan;26(1):98-107. Available on: https://pubmed.ncbi.nlm.nih.gov/24329946/
  13. Garcia-Gutierrez E, Arjan N, Miguel RJ. Autism Spectrum Disorder Associated With Gut Microbiota at Immune, Metabolomic, and Neuroactive Level. Neurosci. 2020;14. Available on: https://www.frontiersin.org/articles/10.3389/fnins.2020.578666/full
  14. Holscher HD. Dietary fiber and prebiotics and the gastrointestinal microbiota. Gut Microbes. 2017;8(2):172-184. Available on: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390821/
  15. McDonnell L, Gilkes A, Ashworth M, et al. Association between antibiotics and gut microbiome dysbiosis in children: systematic review and meta-analysis. Gut Microbes. 2021 Jan-Dec;13(1):1-18. Available on: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7928022/
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