Indomethacin Fails to Increase Intestinal Permeability in Healthy Volunteers

Indomethacin is often used experimentally to induce intestinal hyperpermeability, enabling evaluation of interventions targeting barrier function.

We conducted a randomized, double-blind, placebo-controlled study (NCT05538247) in healthy volunteers to assess whether a supplement could mitigate indomethacin-induced hyperpermeability. Participants received 150 mg/d of indomethacin for 6 days, either before or during placebo/supplement administration. Permeability was measured using 13 C-mannitol and lactulose urinary excretion.

Contrary to expectations, indomethacin failed to increase 13 C-mannitol excretion in either group. No meaningful elevations in serum (zonulin, claudins) or fecal (calprotectin) biomarkers were observed.

Our findings suggest that the expected increase in intestinal permeability after indomethacin administration may not be consistently observed in healthy volunteers. These results highlight the need to carefully consider the reproducibility and sensitivity of this model in future clinical studies aiming to investigate gut barrier function.