Mo2006 Effects of a TGR5 Bile Acid Receptor Agonist and a Dipeptidyl Peptidase-4 Inhibitor on Dextran Sulfate Sodium-Induced Colitis in Mice

Abstract

and by final histology. RESULTS: After ISS-ODN injection, IDO-C but not IDO-KO mice demonstrated increased anxiety behavior as evidenced by less total time in the light box (IDO-C: from 184 to 101 seconds [p=.04] vs. IDO-KO: from 200 to 214 seconds [p=NS]) and less entries into the light box (IDO-C: from 17 to 10.1 entries [p ,.01] vs. IDO-KO from 18.1 to 16.5 entries [p=NS]). Similarly, in response to colitis induction IDO-C mice demonstrated increased anxiety behavior whereas the IDO-KO mice did not. This included fewer entries into the light box (IDO-C: 12.9 vs. IDO-KO: 19.6 entries, p=0.02) and less time in the light box (IDO-C: 224 vs. IDO-KO: 335 seconds, p,0.01). Locomotor differences were not statistically different between groups. These differences in anxiety behaviors were observed even though colitis severity was modestly worse in the IDO-KO group after the third, but not first and second, cycles of DSS. CONCLUSIONS: Increased activity of IDO1 in the gut is associatedwith heightened anxiety behavior patterns in the setting of experimental colitis or after pharmacologic induction. Further investigation to determine the mechanism underlying this observation (decreased serotonin substrate vs. elevated neuroactive kynurenines) is warranted as it may have therapeutic implications for IBD patients affected by disease-activity-related mood disturbance.