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Updated: Jan 3, 2026
Author Spotlight: Developing a Rat Model for Pouchitis Research and Treatment
Published on: May 31, 2024
Preclinical Model of Perianal Fistulizing Crohn's Disease
Meredith Flacs1,2, Maxime Collard1,2, Sabrina Doblas3
1Department of Colorectal Surgery, Assistance Publique Hôpitaux de Paris, Hôpital Beaujon, Clichy la Garenne, Clichy Cedex, France.
Background:
Fistulizing anoperineal lesions (FAPLs) are common and severe complications of Crohn's disease (CD), exposing patients to the risk of anal sphincter alteration and permanent stoma. Due to the limited efficacy of current treatments, identifying new local therapies is mandatory. However, testing new treatments is currently limited because no relevant preclinical model of Crohn's-like FAPL is available. Thus, a reliable and reproducible experimental model of FAPLs is needed to assess new therapeutic strategies.
Methods:
Twenty-one rats received a rectal enema of 2,4,6-trinitrobenzensulfonic acid (TNBS) to induce proctitis. Seven days later, a transsphincteric fistula tract was created with a surgical thread, instilled with TNBS twice a week until its removal at day 7 (group 1), day 14 (group 2), or day 28 (group 3). In each rat, pelvic MRI was performed just before and 7 days after thread removal. Rats were sacrificed 7 days after thread removal for pathological assessment of the fistula tract.
Results:
The optimal preclinical model was obtained in group 3. In this group, 7 days after thread removal, all animals (9 of 9) had a persistent fistula tract visible on MRI with T2-hypersignal (normalized T2 signal intensity: 2.36 ± 0.39 arbitrary units [a.u.] [2.08-2.81]) and elevation of the apparent diffusion coefficient (1.33 ± 0.16 10-3 millimeter squared per seconds [1.18-1.49]). The pathological examination of the fistula tract revealed acute and chronic inflammation, granulations, fibrosis, epithelialization, and proctitis in the adjacent rectum.
Conclusions:
This reproducible preclinical model could be used to assess the effectiveness of innovative treatments in perianal fistulizing CD.
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