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Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism
Abstract
OBJECTIVE: Intestinal permeability and psychological stress have been implicated in the pathophysiology of IBD and IBS. Studies in animals suggest that stress increases permeability via corticotropin-releasing hormone (CRH)-mediated mast cell activation. Our aim was to investigate the effect of stress on intestinal permeability in humans and its underlying mechanisms. DESIGN: Small intestinal permeability was quantified by a 2 h lactulose-mannitol urinary excretion test. In a first study, 23 healthy volunteers were subjected to four different conditions: control; indomethacin; public speech and anticipation of electroshocks. In a second study, five test conditions were investigated in 13 volunteers: control; after pretreatment with disodium cromoglycate (DSCG); administration of CRH; DSCG+CRH and DSCG+public speech. RESULTS: Indomethacin, as a positive comparator (0.071±0.040 vs 0.030±0.022; p<0.0001), and public speech (0.059±0.040; p<0.01), but not the shock protocol increased intestinal permeability. Similarly, salivary cortisol was only increased after public speech. Subgroup analysis demonstrated that the effect of public speech on permeability was only present in subjects with a significant elevation of cortisol. CRH increased the lactulose-mannitol ratio (0.042±0.021 vs 0.028±0.009; p=0.02), which was inhibited by the mast cell stabiliser DSCG. Finally, intestinal permeability was unaltered by public speech with DSCG pretreatment. CONCLUSIONS: Acute psychological stress increases small intestinal permeability in humans. Peripheral CRH reproduces the effect of stress and DSCG blocks the effect of both stress and CRH, suggesting the involvement of mast cells. These findings provide new insight into the complex interplay between the central nervous system and GI function in man.
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“the mechanism appears to rely on intestinal mast cells because it can be abrogated by a mast cell stabilizer (28).”
From Stress triggers flare of inflammatory bowel disease in children and adults (2019) · cites this paper as [28]
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“The results showed that exogenous CRF, as well as psychological stress, can increase the ratio of urine excretion rates of milk fructose and mannitol, showing signs of increased permeability in the small intestine.”
From Stress triggers flare of inflammatory bowel disease in children and adults (2019) · cites this paper as [28]
In the citing paper
“The pressure induced by public speaking enhanced the permeability of the gut only in subjects with significantly elevated cortisol levels, suggesting that HPA axis activation is affected.”
From Stress triggers flare of inflammatory bowel disease in children and adults (2019) · cites this paper as [28]
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Metadata
- Authors
- Vanuytsel, T., van Wanrooy, S., Vanheel, H., Vanormelingen, C., Verschueren, S., Houben, E., Salim Rasoel, S., Tόth, J., Holvoet, L., Farré, R., Van Oudenhove, L., Boeckxstaens, G., Verbeke, K., & Tack, J.
- Affiliations
- Universitair Ziekenhuis Leuven (BE)
- Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium
- KU Leuven (BE)
- Corresponding author
- Tack, Jan
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2013-10-23
- Volume
- 63
- Issue
- 8
- Pages
- 1293-1299
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W2152336072
- Cited by
- 615
- References
- 57
- Citations by year
- 2026: 37 · 2025: 62 · 2024: 57 · 2023: 66 · 2022: 64 · 2021: 61 · 2020: 85 · 2019: 45 · 2018: 40 · 2017: 31 · 2016: 25 · 2015: 22 · 2014: 16 · 2013: 2
- FWCI
- 20.44
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Immunology and Microbiology › Immunology › Mast cells and histamine
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Keywords
- psychological stress, corticotropin-releasing factor, intestinal permeability, mast cells, mast cell stabilizers, disodium cromoglycate, lactulose/mannitol test, salivary cortisol, indomethacin, public speaking, inflammatory bowel disease, irritable bowel syndrome, gut-brain axis
- MeSH terms
- Corticotropin-Releasing Hormone, Cromolyn Sodium, Electroshock, Female, Humans, Hydrocortisone, Indomethacin, Intestine, Small, Lactulose, Male, Mannitol, Mast Cells, Permeability, Saliva, Speech, Stress, Psychological, Young Adult
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