Colonic Ornithine Decarboxylase in Inflammatory Bowel Disease: Ileorectal Activity Gradient, Guanosine Triphosphate Stimulation, and Association with Epithelial Regeneration but Not the Degree of Inflammation and Clinical Features

Abstract

The role of colonic mucosal ornithine decarboxylase (ODC) in inflammatory bowel disease (IBD) remains controversial. This study assessed mucosal ODC activity in IBD patients segment by segment with regard to patient characteristics, disease activity/duration, medication, degree of mucosal inflammation, and presence/absence of epithelial regeneration and guanosine triphosphate (GTP) stimulation. Mucosal ODC activity was determined in biopsy specimens from the terminal ileum, cecum/ascending, transverse, and descending colon, and the sigmoid/rectum of 35 patients with IBD (18 with Crohn's disease, 17 with ulcerative colitis) and 29 controls, using the amount of 14CO2 liberated from (carboxyl-14C)ornithine hydrochloride. GTP-stimulatable activity was expressed as the ratio of ODC activity in the presence and absence of GTP (70 micromol/L). Mucosal inflammation was assessed endoscopically/microscopically with previously described criteria. Presence/absence of mucosal regeneration also was determined by predefined criteria. Mucosal ODC-activity did not significantly differ in IBD patients and controls. There was a 4.4-fold activity gradient from the ileum to the rectum. Mucosal ODC activity was significantly higher in areas with epithelial regeneration compared to those without regeneration, and was stimulated by GTP by a factor of 1.42 in Crohn's disease and 1.19 in ulcerative colitis patients compared to controls (p < 0.004). On the other hand, there was no significant association/relationship of mucosal ODC activity with disease activity/duration and the endoscopic/histologic degree of mucosal inflammation. The observation of unchanged mucosal ODC activity in patients with IBD and the absence of a significant relationship with clinical and endoscopic/histologic disease characteristics speaks against a major role of ODC in IBD as a major disease marker. The role of the ileorectal gradient, the enhanced activity in areas with epithelial regeneration, and the GTP-stimulatable form, however, need further investigation with regard to a possible involvement in carcinogenesis in IBD.

Assessment of Histologic Disease Activity in Crohnʼs Disease

“…This HDAI was later used in a biomarker study attempting to correlate concentrations of colonic mucosal ornithine decarboxylase to CD disease activity and in another study assessing histologic healing with topical glucocorticoids. [11][12][13] The first numerical HDAI was developed by Ward and Webb 42 in 1977 to assess prognosis in patients with CD involving the rectum. These scoring systems have not become widely used in clinical research because they are based exclusively on rectal biopsies, which limit their generalizability to most patients with CD.…”

“…Six features graded as normal (0), mild (1), moderate (2), and severe (3), and summed for a total score corresponding to normal (0-3), mild (4-8), moderate (9)(10)(11)(12)(13)(14), and severe (15)(16)(17)(18) Single prospective study of cytokines in pediatric CD 35 A. Acute inflammatory cell infiltration B.…”

Do biofilms confer a pro-carcinogenic state?

“…A decreasing gradient from the proximal to distal colon in both healthy and disease states has been reported for polyamine levels and ornithine decarboxylase (ODC) prior to our study. 6,7 Our nearly universal detection of biofilms on CRCs in the proximal colon provides additional insight and an explanation for why this gradient might be playing a role in CRC. The idea that a microbial biofilm community, rather than individual organisms, may be primed to differentially produce metabolites that influence carcinogenesis is a new concept that warrants further investigation.…”

ECCO Position on Harmonisation of Crohn’s Disease Mucosal Histopathology

“…49 In a Cochrane review of 14 studies, one study evaluated the terminal ileum exclusively, 69 while nine assessed both terminal ileum and colon. 10,46,65,[70][71][72][73][74][75] Other scoring systems that may be applicable to terminal ileum biopsies in CD include the extent, chronicity, activity plus [ECAP] score 73 and Binder score. 76 In Naini and Cortina's scoring system, the ileum and colon are scored separately.…”

“…Histological scoring systems that were originally developed for the evaluation of UC have been applied to CD intestinal mucosal biopsies. 10,40,46,[69][70][71][72][73][74][77][78][79][80][81][82][83][84][85][86] The Geboes score is the most common in this setting. 22,40,46,69,70,[72][73][74]77,78,86,87 The RHI 10,46,72,73 and Nancy Histological Index 10,73,79 are also used.…”