The Brain in Our Gut

Nishant Mehta Ph.D. candidate

Our nervous system is responsible for receiving sensory impulses from all over the body, processing that information, and then transmitting signals to precisely control organ function. The billions of neurons that make up the human nervous system are finely tuned to provoke change in response to external stimuli[1]. While the power and complexity of the central nervous system (CNS) are well established, the nervous system surrounding the digestive tract is often overlooked. This complex of neurons is called the enteric nervous system (ENS) and controls the coordinated movement required for healthy digestion. Although the ENS usually works in concert with the brain and spinal cord, it also has the ability to function as an independent entity[2], justifying its colloquial name — “the second brain”.

It is all too common for people with digestive issues to hear the phrase “it’s all in your head” and repeatedly be advised to “reduce stress and anxiety”. These warnings have their roots in scientific literature, but are often overused and may not tell the full story. Support for the “all in your head” hypothesis can be found from two key experiments (among many others):

1) rats with early life stressors such as maternal separation showed higher corticosterone (stress hormone) levels and a more drastic stress response than normal rats[3] and 2) IBS patients with higher levels of chronic life stress had significantly higher symptom intensity than patients with lower stress levels[4]. A closer look at the structure of the ENS, however, adds another layer of complexity to the story.

The CNS communicates with the ENS through sympathetic and parasympathetic nerve fibers. Generally, the sympathetic nervous system is responsible for the ‘fight or flight’ response while parasympathetic activation supports ‘rest and digest’ function[5]. One of the largest and most important linkages between the ENS and CNS is the vagus nerve, a key driver of the parasympathetic response. Interestingly, about 90% of the vagus nerve connections between the gut and the brain are afferent, meaning they send signals away from the gut and towards the brain[6]. This structural layout indicates that a significant portion of information originates in the gut and is directed towards the brain, not the other way around. In other words, sensations felt in the digestive tract have a direct line for altering your mood and mental well-being. It is no surprise then, that stimulating the vagus nerve has been found to be an effective treatment for depression[7].

What does this mean for people with digestive issues? The nervous system layout suggests your gut health can have a direct impact on your mental health. For those of us with gut problems, we know this all too well. When we are experiencing a flare-up of gut symptoms, mental problems seem to be magnified — our mood suffers and stress is more difficult to deal with. New evidence suggests that the effect of gut health on the brain goes beyond temporary mood fluctuations and is intricately tied to the gut microbiome[8]. Studies with germ-free mice (mice raised in sterile conditions with no gut bacteria)are being used to examine the effect of changing microbiota on behavior. In adult germ-free mice, mild external stress resulted in an exaggerated release of stress hormone compared to control mice with normal microbiota. This intensified stress response could be fully reversed with administration of commensal bacteria Bifidobacterium infantis[9]. Additionally, increases in chronic gut inflammation through the administration of a mouse parasite Trichus muris significantly increased anxiety-like behavior and could be reversed with anti-inflammatory drugs or probiotics[10].

The jury is still out on exactly how the gut communicates with the brain, whether through vagus nerve innervations or unknown gut-brain modes of interaction. However, a common trend has become clear: gut health has a causal and direct impact on mental health. Next time you hear the phrase “It’s all in your head”, remember that while reducing external stress is clearly important, gut health as a direct driver of mental well-being cannot be overlooked.

References:

[1] R. Lent, F. A. C. Azevedo, C. H. Andrade-Moraes, and A. V. O. Pinto, “How many neurons do you have? Some dogmas of quantitative neuroscience under revision,” Eur. J. Neurosci., vol. 35, no. 1, pp. 1–9, Jan. 2012.

[2] M. Rao and M. D. Gershon, “The bowel and beyond: the enteric nervous system in neurological disorders,” Nat. Rev. Gastroenterol. Hepatol., vol. 13, no. 9, pp. 517–528, Sep. 2016.

[3] S. M. O’Mahony et al., “Early Life Stress Alters Behavior, Immunity, and Microbiota in Rats: Implications for Irritable Bowel Syndrome and Psychiatric Illnesses,” Biol. Psychiatry, vol. 65, no. 3, pp. 263–267, Feb. 2009.

[4] E. J. Bennett, C. C. Tennant, C. Piesse, C.-A. Badcock, and J. E. Kellow, “Level of chronic life stress predicts clinical outcome in irritable bowel syndrome,” Gut, vol. 43, no. 2, pp. 256–261, Aug. 1998.

[5] H. D. Critchley, “Neural mechanisms of autonomic, affective, and cognitive integration,” J. Comp. Neurol., vol. 493, no. 1, pp. 154–166, Dec. 2005.

[6] J. B. Furness, B. P. Callaghan, L. R. Rivera, and H.-J. Cho, “The enteric nervous system and gastrointestinal innervation: integrated local and central control,” Adv. Exp. Med. Biol., vol. 817, pp. 39– 71, 2014.

[7] T. E. Schlaepfer et al., “Vagus nerve stimulation for depression: efficacy and safety in a European study,” Psychol. Med., vol. 38, no. 5, May 2008.

[8] J. F. Cryan and T. G. Dinan, “Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour,” Nat. Rev. Neurosci., vol. 13, no. 10, pp. 701–712, Oct. 2012.

[9] N. Sudo et al., “Postnatal microbial colonization programs the hypothalamic–pituitary–adrenal system for stress response in mice,” J. Physiol., vol. 558, no. 1, pp. 263–275, Jul. 2004.

[10] M. Lyte, W. Li, N. Opitz, R. P. A. Gaykema, and L. E. Goehler, “Induction of anxiety-like behavior in mice during the initial stages of infection with the agent of murine colonic hyperplasia Citrobacter rodentium,” Physiol. Behav., vol. 89, no. 3, pp. 350–357, Oct. 2006.