Fecal DPP4 concentration reflects colonic injury in the TNBS-induced rat model of colitis

Background: Dipeptidyl peptidase 4 (DPP4) is involved in intestinal homeostasis and immune regulation. However, its distribution across biological matrices during intestinal inflammation remains poorly characterized. This study investigated DPP4 concentrations in feces, colonic tissue, and serum in a TNBS-induced rat model of colitis, and assessed host and/or microbiota contribution to fecal DPP4 in knockout and germ-free mice. Methods: Colitis was induced in male Wistar rats by intrarectal administration of an ethanolic solution of TNBS. Disease severity was assessed using clinical evaluation, macroscopic scoring, and histopathological indices. DPP4 concentrations were quantified by ELISA in serum, proximal and distal colonic tissue, luminal content, and cage-collected feces. Colonic DPP4 location was assessed by immunohistochemistry. To explore host and microbiota contributions, fecal DPP4 concentration was also measured in DPP4 knockout and germ-free mice. Results: TNBS-induced colitis resulted in regionally heterogeneous inflammation, predominantly affecting the distal colon. In healthy rats, colonic DPP4 showed a proximal-to-distal gradient that was lost during inflammation. Fecal DPP4 concentrations were significantly increased in TNBS-treated animals, exhibited a proximal-to-distal increase, and reached highest levels in cage fecal pellets. Fecal DPP4 correlated with macro and microscopic scores, and with distal colonic DPP4 levels, whereas serum DPP4 did not differ between groups. Fecal DPP4 levels were reduced in DPP4 knockout and germ-free mice, suggesting a modulation of fecal DPP4 by a host-microbiota crosstalk. Conclusions: DPP4 distribution is context- and matrix-dependent. Fecal DPP4 reflects regional and histological features of experimental colitis, by integrating local intestinal injury with luminal shedding.