Lupianez-Merly, Camille

INTRODUCTION: Indomethacin is often used experimentally to induce intestinal hyperpermeability, enabling evaluation of interventions targeting barrier function. METHODS: 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. RESULTS: 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. DISCUSSION: 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.

ABSTRACT Background Bile acid diarrhoea, a common cause of diarrhoea‐predominant irritable bowel syndrome, has a similar prevalence to coeliac disease and inflammatory bowel diseases. The mainstay of treatment is bile acid sequestrants (BAS). The effectiveness of using bile acid‐targeted therapies remains unclear. Aim To compare BAS with placebo for bile acid diarrhoea. Methods We conducted a systematic review and meta‐analysis of randomised controlled trials comparing BAS to placebo using a comprehensive search of databases from inception to 8/1/2023. Inclusion required unequivocal diagnosis using serum or faecal biochemical parameters, or 75 SeHCAT. Co‐primary endpoints were ≥ 30% improvement in bowel movement consistency and frequency averaged over 7 days. Adverse effects were also summarised. Results Database search resulted in 1152 citations; 1 additional study was added. Ultimately, 6 trials (5 parallel arm, 1 crossover) involving 182 participants evaluated the effectiveness of BAS over 1–8 weeks. Participants were between the third and seventh decades of life and mostly female. The risk of bias was low except in one parallel and one crossover trial. Meta‐analysis of parallel‐design trials of sequestrants only showed a clinically significant reduction in stool consistency and frequency with pooled relative risks of 1.50 (95% CI: 1.14–1.96) and 2.80 (95% CI: 1.68–4.67), respectively. There was no observable heterogeneity ( I 2 = 0%), and the certainty of evidence was moderate. There was no statistically significant difference in adverse effects. Conclusions This study quantifies the significant and rapid improvement in both stool consistency and frequency with BAS in patients with objective diagnosis of bile acid diarrhoea. Sequestrants also appear well tolerated.