What is Enteric Nervous System?

The enteric nervous system (ENS) had been regarded as a digestive organ till; the remarkable discovery made by Michael Gershon that 90% of the body’s serotonin is located within the walls of the gastrointestinal (GI) tract. This ignited interests of various neuroscientists, including psychiatrists, about the GI nervous system. The enteric nervous system is composed of neuronal plexuses like the Meissners and Auerbach’s plexus that has a pool of more than 30 neurotransmitters like serotonin, dopamine, glutamate, norephinephrine and nitric oxide, and other chemical mediators like neuropeptides and enkephalins. It also contains glia-like supportive cells, and together contains nearly 100 million neurons as that in the spinal cord. As a result, the enteric nervous system is now called the second brain as it can function of its own without the need of the brain.

What is Gut-Brain axis?

The Gut-Brain Axis describes the bi‐directional neural pathways linking cognitive and emotional centers in the brain to the enteric nervous system.

Can psychosocial stress damage gut brain axis?

Emotional states such as depression and behavioral dispositions, ranging from hostility to psychosocial stress, can directly influence both physiologic function and health outcomes in different ways. One such example is the Gut Brain Connection. The gut brain connection is intimately involved in explaining how the psychosocial stress – induced inflammatory response in the gut – is modulated by the bidirectional communication between the guts enteric nervous system with brain. Many lines of research have established multiple pathways by which the immune system and the enteric nervous system communicate bidirectionally with the brain. The enteric nervous system communicates with CNS through neural, immune and endocrine pathways which may help in understanding the mind-body connection.

How psychosocial stress can damage Gut-Brain axis?

 
The normal gut flora is essential to maintain the Gut brain axis, thereby maintaining a good mood. The composition of normal gut flora varies from person to person. Any disruption in the growth of normal microbes impairs cognitive and emotional balance. Whenever the gut is exposed to pathogenic microbes; secretory IgA is constantly produced (60 mg/kg) at the gastrointestinal interface by plasma cells to prevent adhesion of these pathogens, thus maintains a homeostatic gut brain axis. But during stress, the IgA production is decreased due to the stress hormones like cortisols inhibiting the plasma cells that produces the IgA antibodies and in addition it also leads to the activation of pro-inflammatory cytokines like Tumor Necrosis Factor Alpha and Interleukins‐1,6,8 which spontaneously stimulates the hypothalamus in the brain to produce parent stress hormones like Corticotrophin releasing hormones (CRH) via two routes : (a) crossing blood brain barrier (a barrier that protects the brain from toxins) via blood stream and (b) Vagus nerve which carries 90% of information of immune status from periphery to CNS. The CRH thus produced in turn stimulates ACTH from anterior pituitary simulates the Adrenal cortex to produce cortisols.

References

1. Gershon M. The second brain: a groundbreaking new understanding of nervous disorders of the stomach and intestine. New York, NY: HarperCollins Publishers; (1998).
2. McMillin DL, Richards DG, Mein EA, Nelson CD. The abdominal brain and enteric nervous system. J Altern Complement Med. (1999); 5(6):575-86.
3. Wood JD, Alpers DH, Andrews PLR. ​Fundamentals ​of neurogastroenterology. Gut(1999); 45(Suppl II):II6 – II16.
4. Shanahan F. Brain-gut axis and mucosal immunity: a perspective on mucosal psychoneuroimmunology. Semin Gastrointest Dis.(1999) Jan;10(1):8-13.
5. Anton V L, Cortizo B : Mind-Body Medicine: Stress and Its Impact on Overall Health and Longevity. Ann. N.Y. Acad. Sci.1057: 492 – 505 (2005). doi:10.1196/annals.1322.038
6. De Kloet ER, Oitzl MS, Schobitz B. Cytokines and the brain corticosteroid receptor balance: relevance to pathophysiology of neuroendocrine-immune communication. Psychoneuroendocrinology. (1994);19(2):121-34.
7. Serotonin, tryptophan metabolism and the brain-gut-microbiome axis: S.M. O’Mahony, G. Clarke, Y.E. Borre, T.G. Dinan, J.F. Cryan: Behavioural Brain Research. Elsevier 277 (2015) 32 – 48
8. Cunningham-Rundles C. Physiology of IgA and IgA deficiency. J Clin Immunol.(2001); 21 :303 – 309
9. Bosch JA et al, Depressive symptoms predict mucosal wound healing. Psychosom Med.(2007) Sep-Oct;69(7):597-605. Epub (2007) Aug 31.
10. Watkins L R, Maier S F. Implications of immune-to-brain communication for sickness and pain PNAS 96: 7710-7713.(1999)
11. Turnbull AV, Rivier C Regulation of the HPA axis by cytokines. Brain Behav Immun, Dec (1995); 9(4): 253-75.
12. Sternberg, E M. Neural-immune Interactions in Health and Disease J. Clin. Invest. (1997) 100: 2641-2647
13. Kiank C, Zeden J-P, Drude S, Domanska G, Otten W, et al. (2010)Psychological Stress induced IDO1- Dependent Tryptophan Catabolism: Implications oon immunesuppression in Mice and Humans. PLos ONE 5(7): e11825. Doi: 10.1371/journal.pone.0011825