Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism.
Level 3 - non-randomized controlled study
Controlled experimental human crossover challenge studies without reported randomization details in the abstract
PubMed 24153250 · doi:10.1136/gutjnl-2013-305690
What was done
Small intestinal permeability was measured using a 2-hour urinary lactulose-mannitol excretion test across two human challenge experiments. In Study 1, 23 healthy volunteers were tested across four conditions: baseline control, indomethacin (positive control), public speaking stress, and anticipation of electroshocks, alongside salivary cortisol measurements. In Study 2, 13 healthy volunteers were evaluated across five conditions: control, pretreatment with the mast cell stabilizer disodium cromoglycate (DSCG), administration of corticotropin-releasing hormone (CRH), DSCG plus CRH, and DSCG plus public speech.
What was found
Indomethacin increased the lactulose-mannitol ratio from 0.030 ± 0.022 to 0.071 ± 0.040 (p < 0.0001). Public speaking increased permeability to 0.059 ± 0.040 (p < 0.01), whereas anticipation of electroshocks did not. Salivary cortisol rose only after public speaking, and subgroup analysis showed the permeability increase was present only in subjects with a significant elevation of cortisol. CRH administration increased the lactulose-mannitol ratio from 0.028 ± 0.009 to 0.042 ± 0.021 (p = 0.02). Pretreatment with DSCG blocked both the CRH-induced and public speech-induced increases in permeability.
Why it matters
This study provides direct experimental evidence in humans that acute psychological stress elevates intestinal permeability via CRH and mast cell activation. This helps explain the mechanistic bridge between central nervous system stress and gut barrier dysfunction relevant to irritable bowel syndrome and inflammatory bowel disease.
Limits
Sample sizes were very small (23 and 13 participants), and the study tested acute laboratory stressors in healthy volunteers rather than chronic real-world stress or patients with clinical bowel disease. The abstract does not report whether sequence allocation was randomized or blinded.
Cited by
- supports Psychological stress, such as defending a college thesis during an oral examination, rapidly increases intestinal permeability, anxiety, and cortisol levels.