CoChat
Sign Up
Cited by 666Gastrointestinal motility and disordersStress Responses and CortisolPsychosomatic Disorders and Their Treatments

The neurobiology of stress and gastrointestinal disease

Open access
MAYER, E A·2000·Gut
DOI 10.1136/gut.47.6.861PMC PMC1728136
Open this paper in CoChat — free accountOpen PDF

Abstract

The role of stress in the modulation of the most common gastrointestinal disorders has traditionally been considered a domain of psychology, and has frequently been lumped together with the role of psychiatric comorbidity. Among clinicians, the term “stress” is generally taken as synonymous with psychological (“exteroceptive”) stress. Based on the deeply ingrained Cartesian view in medicine and gastroenterology, stress and psychological factors have been considered fundamentally separate and unrelated to the “real” biological changes underlying organic disease. However, recent breakthroughs in the understanding of the neurobiology of the organism's response to acute and chronic stress, and the evolving understanding of elaborate brain-gut interactions and their modulation in health and disease, are beginning to require a reassessment of chronic stress in the pathophysiology and management not only of functional but also of “organic” gastrointestinal disorders. Certain stressful life events have been associated with the onset or symptom exacerbation in some of the most common chronic disorders of the digestive system, including functional gastrointestinal disorders (FGD), inflammatory bowel disease (IBD), gastro-oesophageal reflux disease (GORD), and peptic ulcer disease (PUD). Even though methodological differences in reported studies which do and do not support such an association remain to be resolved, the association of sustained stressful life events preceding symptom exacerbation is based on several well designed surveys in patients with FGD,1-4with post-infectious irritable bowel syndrome (IBS),4 and with IBD.5-8 In addition, acute life threatening stress episodes in adult life (rape, post-traumatic stress syndrome) are an important risk factor in the development of functional gastrointestinal disorders.9 Finally, early life stress in the form of abuse plays a major role in the susceptibility of individuals to develop functional as well as IBD10-14 later in life. Thus, depending on the type of stressor, the lag time between the stressful event …

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1136/gut.47.6.861

Cites

162 of 162 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Studies showed that distention of the gut resulted in activation of key pathways within the brain and that such pathways are exaggerated in disorders such as irritable bowel syndrome.

    “Studies showed that distention of the gut, resulted in activation of key pathways within the brain and that such pathways are exaggerated in disorders such as irritable bowel syndrome (IBS), a functional GI disorder with dysregulated microbiota-gut-brain axis (Farmer and Aziz, 2014;Kennedy et al., 2014;Mayer, 2000).”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Mayer, 2000

    In “CHANGES IN BRAIN ACTIVATION” (page unavailable), the paper reports brain activation patterns during rectal distension, supporting the first part of the claim. It does not report exaggerated activation of those pathways in IBS: the preliminary comparison found similar patterns overall and decreased activation in several regions in IBS patients. The cited passage also does not establish the sentence’s microbiota–gut–brain-axis characterization. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The HPA axis is one of the main neuroendocrine systems in the human body and one of the key non-neuronal routes of communication within the microbiota-gut-brain axis.

    “The HPA axis is one of the main neuroendocrine systems in the human body and one of the key non-neuronal routes of communication within the microbiota-gut-brain axis.”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Mayer, 2000

    The HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS and Physical and psychological stressors sections describe the HPA axis as a hormonal stress-response pathway involved in brain–gut interactions. They do not identify it as a key non-neuronal communication route within a microbiota–gut–brain axis or establish its relative importance among such routes. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • The primary function of HPA axis activation is to prime the body for the 'fight or flight' response.

    “The primary function of the HPA axis activation is to prime the body for the 'fight or flight' response (Mayer, 2000).”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Mayer, 2000

    The HPA-axis section says the axis is activated by acute stressors, supporting its involvement in the stress response. But the section on modulation of physiological stress responses associates “fight and flight” with sympathetic nervous-system activation, while the HPA-axis section emphasizes suppression of inflammation. The paper does not identify priming the body for fight or flight as the HPA axis’s primary function. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • The HPA axis is the principal neuroendocrine coordinator of the response to stress.

    “It is best known as the principal neuroendocrine coordinator of the response to stress (Mayer, 2000).”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Mayer, 2000

  • Cortisol receptors are expressed on various cells of the gut, including epithelial cells, immune cells, and enteroendocrine cells, indicating a direct effect of cortisol on gut function.

    “Cortisol receptors are expressed on various cells of the gut, including epithelial cells, immune cells, and enteroendocrine cells, indicating a direct effect of cortisol on gut function (21, 29, 48).”

    From Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis (2023) · cites this paper as [48]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 27

  1. Pomakov P, Gueorgieva S, Stantcheva J, et al. Ulceres gastro-duodenaux pendant la periode d'une crise economique aigue. J Radiol 1993;74:265-7.
  2. Peterson WL, Graham DY. Helicobacter pylori In: Feldman M, Scharschmidt B, Sleisenger MH, eds. Gastrointestinal and liver disease: pathophysiology, diagnosis, management, 6 edn. Philadelphia: WB Saunders, 1997:604-19.
  3. Chrousos GP, Loriaux DL, Gold PW. The concept of stress and its histori- cal development. Adv Exp Med Biol 1988;245:3-7.
  4. Eley TC, Plomin R. Genetic analysis of emotionality. Curr Opin Neurobiol 1997;7:279-84.
  5. Heim C, Newport DJ, Heit S, et al. Pituitary-adrenal responses to CRF stimulation in adult survivors of childhood abuse with and without depres- sion. Soc Neurosci Abstr 1999;25:1454.
  6. Bremner JD, Narayan M, McGlashan J, et al. Lasting eVects of early child- hood sexual abuse on the hypothalamic-pituitary-adrenal axis. Soc Neurosci Abstr 1999;25:1454.
  7. Stamm R, Yehuda R, Giller EL Jr, et al. Hypothalamic-pituitary-adrenal functioning in post-traumatic stress disorder: expanding the concept of the stress response spectrum In: Friedman MJ, Charney DS, Deutch AY, eds. Neurobiological and clinical consequences of stress. Philadelphia: Lippincott- Raven, 1995:351-66.
  8. Taylor SE. Adjusting to threatening events: A theory of cognitive adaptation. Am Psychol 1983;41:1161-73.
  9. Plotsky PM, Cunningham ET, Widmaier EP. Catecholaminergic modula- tion of corticotropin-releasing factor and dexamethasone secretion. Endocrinol Rev 1989;10:437-58.
  10. Yehuda R, Giller EL, Levengood RA, et al. Hypothalamic-pituitary-adrenal functioning in post-traumatic stress disorder: Expanding the concept of the stress response spectrum. In: Friedman MJ, Charney DS, Deutch AY, eds. Neurobiological and clinical consequences of stress: from normal adaptation to PTSD, vol. 19. Philadelphia: Lippincott-Raven, 1995:351-65.
  11. Jaenig W, Habler H-J. Mayer EA, et al, eds. The biological basis for mind body interactions, 122 edn. Amsterdam: Elsevier Science, 2000:349-65.
  12. Berin MC, Perdue MH. EVect of psychoneural factors on intestinal epithe- lial function. Can J Gastroenterol 1997;11:353-7.
  13. Felten DL, Mayer EA, Saper CB, eds. The biological basis for mind body inter- actions, vol. 27, 122 edn. Elsevier Science, 2000:379-87.
  14. Felten SY, Felten DL, Ader R, et al, eds. Psychoneuroimmunology, 2 edn. San Diego: Academic Press, 1991:27-69.
  15. Peristein RS, Whitmall MH, Abrams JS, et al. Syndergistic roles of interleukin-6, interleukin-1 and tumor necrosis factor in adrenocorticotro- pin response to bacterial lipopolysaccharide in vitro. Endocrinology 1993;132:946-52.
  16. Kemeny ME, Gruenwald TL, Mayer EA, et al, eds. The biological basis for mind body interactions, vol. 21, 122 edn. Amsterdam: Elsevier Science, 2000: 289-306.
  17. Verrier RL, Mittleman MA, Mayer EA, et al, eds.The biological basis for mind body interactions, vol 26, 122 edn. Amsterdam: Elsevier Science, 2000:367- 78.
  18. Musselman D, NemeroV CB, Mayer EA, et al, eds. The biological basis for mind body interactions, vol. 5, 122 edn. Amsterdam: Elsevier Science, 2000: 43-58.
  19. McEwen BS, Friedman JM, Charney DS, et al, eds. Neurobiological and clini- cal consequences of stress: from normal adaptation to PTSD. Philadelphia: Lippincott-Raven, 1995:135-50.
  20. McEwen BS, Mayer EA, Saper CB, eds. The biological basis for mind body interactions, 122 edn. Amsterdam: Elsevier, 2000. 102
  21. Coutinho SV, Miller JC, Plotsky PM, et al. EVect of perinatal stress on responses to colorectal distension in adult rats. J Neurosci 1999;25:687. 111
  22. Moldofsky H, Franklin LA, Mayer EA, et al, eds. Basic and clinical aspects of chronic abdominal pain. New York: Elsevier, 1993:249-56. 143
  23. Spiller RC, Thornley JP, Neal K, et al. Acute and chronic enteroendocrine cell hyperplasia and increased gut permeability in post-dysenteric bowel dysfunction. Gastroenterology 1999;116:A1086. 145
  24. Rao SCC, Holdsworth CD, Read NW. Anorectal sensitivity and reactivity in patients with ulcerative colitis. Gastroenterology 1987;93:1270-5. 162
  25. Chang L, Munakata J, NaliboV BD, et al. DiVerences in perceptual responses to rectosigmoid stimulation in mild ulcerative colitis and irritable bowel syndrome. Gut 2000 (in press). 163
  26. Chang L, Derbyshire SW, Munakata J, et al. Perceptual and CNS Responses to visceral pain in patients with inflammatory bowel disease. Soc Neurosci 1999;25:1045. 166
  27. Fass R, Malagon I, NaliboV BD, et al. EVect of psychologically induced stress on symptom perception and autonomic nervous system response of patients with erosive esophagitis. Gastroenterology 2000;118:A637. 169

Cited by

Sorted by citations

Related

Authors
MAYER, E. A.
Affiliations
University of California, Los Angeles (US)
Corresponding author
MAYER, E A
ORCID
MAYER, E A
Venue
Gut
Publisher
BMJ
Published
2000-12-01
Volume
47
Issue
6
Pages
861-869
ISSN
  • 0017-5749 (ISSN-L)
  • 1468-3288
DOI
10.1136/gut.47.6.861
PMC
PMC1728136
OpenAlex
W2130721477
Cited by
666
References
162
Citations by year
2026: 18 · 2025: 27 · 2024: 36 · 2023: 23 · 2022: 38 · 2021: 32 · 2020: 20 · 2019: 25 · 2018: 38 · 2017: 36 · 2016: 33 · 2015: 28 · 2014: 28 · 2013: 21 · 2012: 25
FWCI
3.34
Type
journal article
Language
en
Open access
Locations
  • Gut (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Topics
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
Keywords
stress, neurobiology of stress, gastrointestinal diseases, gut-brain axis, functional gastrointestinal disorders, inflammatory bowel disease, gastroesophageal reflux disease, peptic ulcer, irritable bowel syndrome, life events, early life stress, post-traumatic stress, psychiatric comorbidity
MeSH terms
Adaptation, Physiological, Adaptation, Psychological, Autonomic Nervous System Diseases, Gastrointestinal Diseases, Homeostasis, Humans, Stress, Mechanical, Stress, Psychological

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review