Stress is something that most people have to deal with on a daily basis. Appropriate levels of stress promote powerful benefits throughout the body, yet when the systems associated with stress are routinely activated, the body may not respond as we would like.
In response to stress, the hormone corticotrophin-releasing factor (CRF) is released from the hypothalamus. A primary function of CRF is to act on the anterior pituitary to stimulate the release of adrenocorticotropic hormone (ACTH), which in turn stimulates the synthesis of cortisol, glucocorticoids, mineralocorticoids, and DHEA.1 While CRF is very important for the acute stress response, its presence can have some potent effects throughout the body.
The effects of stress throughout the body are quite pervasive and the effects of stress on digestion can be widely occurring with several discussed below.
Intestinal Permeability
Tight junction proteins include claudin-1, occludin, and zona occludens-1 (also known as tight junction protein1). A significant decrease in their expression was noted in rats following chronic corticosterone injections. The healthy expression of the three proteins is important in maintaining intestinal permeability.2
If you are not intimately familiar with these proteins and the clinical application of them, you are not alone. These are relatively new therapeutic targets thanks in large part to the late Shoichiro Tsukita and his successors.3,4 The higher the levels of these are, the “tighter” the paracellular junctions are and the less likely antigen proteins would interact with the immune system.
Gut Motility
Motility (the contraction of the muscles that mix and propel contents in the gastrointestinal (GI) tract) is an important aspect of healthy digestive function. The efficient movement of ingested nutrients promptly supports appropriate digestive processes and proper microbial diversity.
A mouse model demonstrated that healthy motility resulted in appropriate gut microbial distributions.5 Receptors to CRF exist throughout the digestive tract, and when activated, affect gut motility. Receptors are also present in the central nervous system in which their activation results in delayed gastric emptying.6
Colon Inhibition
Studies suggest that the stress response impacts the powerful system referred to as the gut-brain axis. A 2016 study suggests that myenteric neurons can be signaled resulting in increased inhibitory neuromuscular transmission, impacting bowel transit time.7 In this animal model, one cellular mechanism of stress and bowel function were demonstrated. In this case, the model stress causes decreased transit time and diarrhea.
Visceral Hypersensitivity
In rat models, CRF was shown to activate myenteric neurons and increase neuronal excitability of colonic tissue.8 This sheds new light on the interplay between the immune system and specific cytokines with the functioning of the bowel. Indeed, a multipronged approach to support bowel function may be necessary which includes addressing systems that interact with the gut either at an intimate level or rather remotely. What is fascinating about this particular study is that both the immune-mediated factors and stress-mediated factors had to be mitigated in order to restore homeostasis in the model.
Sleep Disruption and Cytokines
The HPA axis and sleep are closely associated and carry powerful influence over each other. Repeated HPA axis activation can have a detrimental effect on sleep quality and maintaining healthy circadian cycles. The cytokines IL-6 and TNF-α have been shown to increase in response to poor sleep cycles.9 The same cytokines have also been implicated in a variety of digestive health concerns.10
How to Overcome the Effects of Stress on Digestion
In practice, I consistently encounter people who live a high-stress life and frequency report that digestive function is suboptimal or distressing. As I hear their concerns, I cannot help but pursue options which can improve one’s tolerance to stress while directly supporting healthy digestive function.*
- Manage stress with appropriate lifestyle modifications (Each patient has their own optimal lifestyle prescription to manage stress but ultimately, it comes down to sleep, relaxation techniques, remaining well-nourished, and attitude factors. Mindful meditation is a powerful option, which demonstrates improved responses to stressful stimuli.)11
- Modulation of the stress response with adaptogenic herbs*12,13
- Support of healthy circadian cycles and promotion of sleep14,15
- Support motility with ginger,16 artichoke,17 D-limonene,18 and 5-HTP*19
- Intestinal mucosa support with L-Glutamine20 and N-Acetyl D-Glucosamine*21
- Support cytokine balance with EPA, DHA,22 and curcumin*23
Promoting healthy stress tolerance and optimal GI function can be difficult. I have found that prioritizing the aspects of digestion based on individual needs has resulted in consistently positive outcomes in my patients. Resources such as the Gastrointestinal Restoration Program provide me with a foundation to guide my recommendations and help me to prioritize aspects which are most important to an individual’s plan. Integrating this program into my practice was effortless and rounded out my supplement recommendations to address patients’ different needs.
REFERENCES
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- Zheng G et al. Neurogastroenterol Motil. . 2013;25(2):e127-39.
- Takeichi M. J Cell Biol. 2006 Jan 30;172(3):321-3.
- Anderson JM. Ann N Y Acad Sci. 2009 May;1165:7-9.
- Wiles TJ et al. PLoS Biol. 2016 Jul;14(7): e1002517.
- Chang Y-M et al. Expert Rev Gastroenterol Hepatol. 2014;8(6):583-5.
- Reed DE et al. Neurogastroenterol Motil.. 2016 Apr;28(4): 569-80.
- Buckley MM et al. J Physiol. 2014;592(Pt 23):5235-50.
- Chrousos et al. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279071.
- Ali T et al. World Journal of Gastroenterology : WJG. 2013;19(48):9231-9.
- Gotink RA et al. 8-week Mindfulness Based Stress Reduction. Brain and Cognition. 2016 Oct;108:32-41. doi: 10.1016/j.bandc.2106.07.001.
- Pratte MA et al. J Altern Complement Med.. 2014;20(12):901-8.
- Jyoti S et al. Methods Find Exp Clin Pharmacol. 2007 Jul-Aug;29(6):411-6.
- Kolbe I et al. Int J Endocrinol. 2015;2015:693204.
- Konturek PC, Brzozowski T, Konturek SJ. Gut clock: implication of circadian rhythms in the gastrointestinal tract. J Physiol Pharmacol. 2011;62:139–50.
- Hu M-L et al. World J Gastroenterol. 2011 Jan 7;17(1):105-10.
- Lazzini S et al. Eur Rev Med Pharmacol Sci. 2016;20(1):146-9.
- Sadraei H et al. Res Pharm Sci. 2015 Mar-Apr;10(2):109-16.
- Sanger GJ et al. Eur J Pharmacol. 1986 Aug 15;127(3):179-85.
- Wang B et al. Amino Acids. 2015 Oct;47(10):2143-54.
- Salvatore S et al. Aliment Pharmacol Ther. 2000;14(12):1567-79.
- Calder PC. Biochim Biophys Acta. 2015 Apr;1851(4):469-84.
- Sahebkar A et al. Pharmacol Res. 2016 May;107:234-42.