How Stress Changes Gut Function

Over the past few decades, researchers have worked to unravel the delicate connections between the human gastrointestinal microbiota and the brain, and there has been a growing emphasis on the way that psychological stress affects gastrointestinal function. Studies suggest that stress-mediated changes, like changes in the level of catecholamines including norepinephrine, may shift the microbial colonization patterns on the mucosal surface of the intestine and alter one’s susceptibility to infection.1 Changes in this environment may lead to a spectrum of other physiological changes, including hypothalamic-pituitary-adrenal (HPA) axis activation and altered autonomic nervous system (ANS) responses.2

Research suggests that irritable bowel syndrome (IBS) may be a stress-sensitive disorder.3 A 2013 study showed that IBS patients had ANS dysregulation prior to, during, and after a visceral stressor; this autonomic dysregulation was more pronounced in patients who had the disease for a greater period of time.3 The principal effectors of the stress system are corticotropin-releasing hormone, arginine vasopressin, proopiomelanocortin-derived peptides, alpha-melanocyte-stimulating hormone and beta-endorphin, glucocorticoids, and the catecholamine hormones norepinephrine and epinephrine.4

In the following video, IFM educator Vincent Pedre, MD, talks about the connection between stress and gastrointestinal function:

Vincent Pedre, MD, is a board-certified internist practicing in New York City.

Research suggests that episodes of anxiety and depression may be experienced more frequently in patients with gastrointestinal disorders like IBS.5 Negative emotions, stressful life events, and personality traits like neuroticism have also been associated with colitis and Crohn’s disease.5 In one study, patients experiencing intense and prolonged stressful life events had a 90% recurrence rate of their colitis as compared to only a 40% recurrence in low-stress patients.6 Early life stress and trauma, in the form of abuse, neglect, or loss, contribute to the development of gastrointestinal disorders.2,4,5 Acute life-threatening stress episodes in adult life (rape, post-traumatic stress disorder) are also important risk factors for gastrointestinal disorders.2

Stress also plays a central role in another common gastrointestinal disorder, functional dyspepsia (FD).7 Utilizing the Buspirone Neuroendocrine challenge test, researchers have shown that FD patients have hypersensitive central 5-HT (serotonin) receptors.5 5-HT serves multiple functions in the human brain and is involved in the control of emotions, endocrine responses, stress coping, and aggression.8 A 2017 study suggests a “brain circuit in which serotonin neurons in the dorsal raphe depending on the CRF (corticotropin releasing factor) regulatory action engage a prefrontal cortical-amygdala pathway through 5-HT1A receptors, GABA and Glutamate to moderate coping behavior.”8 5-HT plays an important role in the control of gastrointestinal function, both peripherally and centrally. Similarly, research suggests that the hypersensitivity of the central 5-HT receptors are highly correlated with delayed gastric emptying.5

Peripheral outputs of the stress response, in particular glucocorticoids and catecholamines, have an effect on cytokine networks, including those in the gut mucosa.2 Stress influences the production of key regulatory type 1 and type 2 cytokines, T helper Th1 and Th2 functions, and components of cellular and humoral immunity. In the healthy organism, both glucocorticoids and catecholamines suppress Th1 responses and cellular immunity and shift the immune response toward Th2 responses and humoral immunity. In contrast, in Crohn’s disease, the response pattern is shifted toward Th1 responses. Based on these observations, researchers speculate that the different patterns of the stress response in chronic functional and inflammatory conditions of the gut may have opposite effects on the Th1/Th2 balance in the gut mucosa.2

A number of studies have investigated the effect of prebiotic and probiotic intervention on emotional dysregulation.2 Using cortisol as an index of stress response, the probiotics Lactobacillus helveticus and Bifidobacterium longum as well as galactooligosaccharide prebiotic were effective in boosting the subjects’ resilience to stress and improved emotional responses.2 A 2015 study suggests that prebiotic administration of bimuno-galactooligosaccharides reduces the salivary cortisol awakening response in healthy people.8 Ingestion of a specific probiotic cocktail was shown to alter brain activity and informational processing of emotional material in a functional magnetic resonance imaging brain scan study, as well as reducing negative thoughts associated with sad mood, further reinforcing the role for gastrointestinal microbiota in stress and emotional responses.2

A 2016 double-blind, placebo-controlled study found that the daily consumption of probiotics such as the Lactobacillus casei strain Shirota preserves the diversity of the gut microbiota and may relieve stress-associated responses of abdominal dysfunction in healthy subjects exposed to stressful situations.9

Exercise is another non-pharmacological strategy that may mitigate the detrimental impact of stress.10 New evidence suggests that both prebiotic diets and exercise interventions are most effective if given early in life when the gut and brain are more plastic.10 In adults, replacing a Western diet with one high in fiber, protein, and vegetarian dietary patterns has been shown to be beneficial for healthy gastrointestinal function.11

What other dietary and lifestyle interventions can help to diminish the effects of stress within the body and affect gastrointestinal function? Learn more in the GI Advanced Practice Module.

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  1. Lyte M, Vulchanova L, Brown DR. Stress at the intestinal surface: catecholamines and mucosa-bacteria interactions. Cell Tissue Res. 2011;343(1):23-32. doi:10.1007/s00441-010-1050-0.
  2. Rea K, Dinan TG, Cryan JF. The microbiome: a key regulator of stress and neuroinflammation. Neurobiol Stress. 2016;4:(23-33). doi:10.1016/j.ynstr.2016.03.001.
  3. Cheng P, Shih W, Alberto M, et al. Autonomic response to a visceral stressor is dysregulated in irritable bowel syndrome and correlates with duration of disease. Neurogastroenterol Motil. 2013;25(10):e650-e659. doi:10.1111/nmo.12177.
  4. Charmandari E, Kino T, Souvatzoglou E, Chorousos GP. Pediatric stress: hormonal mediators and human development. Horm Res. 2003;59(4):161-179. doi:10.1159/000069325.
  5. Panduro A, Rivera-Iniguez I, Sepulveda-Villegas M, Roman S. Genes, emotions, and gut microbiota: the next frontier for the gastroenterologist. World J Gastroenterol. 2017;23(17):3030-3042. doi:10.3748/wjg.v23.i17.3030.
  6. Hollander D. Inflammatory bowel diseases and brain-gut axis. J Physiol Pharmacol. 2003;54(Suppl 4):183-190.
  7. Chua ASB, Keeling PWN. Cholecystokinin hyperresponsiveness in functional dyspepsia. World J Gastroenterol. 2006;12(17):2688-2693. doi:10.3748/wjg.v12.i17.2688.
  8. Puglisi-Allegra S, Andolina D. Serotonin and stress coping. Behav Brain Res. 2015;277:58-67. doi:10.1016/j.bbr.2014.07.052.
  9. Kato-Kataoka A, Nishida K, Takada M, et al. Fermented milk containing Lactobacillus casei strain Shirota preserves the diversity of the gut microbiota and relieves abdominal dysfunction in healthy medical students exposed to academic stress. Appl Environ Microbiol. 2016;82(12):3649-3658. doi:10.1128/AEM.04134-15.
  10. Mika A, Rumian N, Loughridge AB, Fleshner M. Exercise and prebiotics produce stress resistance: converging impacts on stress-protective and butyrate-producing gut bacteria. Int Rev Neurobiol. 2016;131:165-191. doi:10.1016/bs.irn.2016.08.004.
  11. Conlon M, Bird AR. The impact of diet and lifestyle on gut microbiota and human health. Nutrients. 2014;7(1):17-44. doi:10.3390/nu7010017.

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