Indomethacin Fails to Increase Intestinal Permeability in Healthy Volunteers

Area of Science:

• Gastroenterology
• Pharmacology
• Clinical Research

Background:

• Indomethacin is commonly used to induce intestinal hyperpermeability in experimental settings.
• This model allows for the evaluation of interventions aimed at improving gut barrier function.

Purpose of the Study:

• To assess if a supplement could mitigate indomethacin-induced intestinal hyperpermeability in healthy volunteers.
• To evaluate the reliability of indomethacin as a model for inducing gut barrier dysfunction.

Main Methods:

• A randomized, double-blind, placebo-controlled study (NCT05538247) was conducted.
• Participants received indomethacin (150 mg/d for 6 days) with either placebo or a supplement.
• Intestinal permeability was measured using 13C-mannitol and lactulose urinary excretion.

Main Results:

• Indomethacin administration did not significantly increase 13C-mannitol excretion.
• No substantial changes were observed in serum biomarkers (zonulin, claudins) or fecal calprotectin.
• The expected indomethacin-induced hyperpermeability was not reliably reproduced.

Conclusions:

• The findings question the consistent efficacy of indomethacin in inducing intestinal hyperpermeability in healthy individuals.
• The study underscores the need for careful consideration of the reproducibility and sensitivity of this model in future gut barrier research.
• Results suggest potential limitations in using indomethacin for evaluating gut barrier interventions in clinical studies.