P039 Suppression of phospholipase A2 of intestinal microbiota by the phospholipid-bile acid conjugate ursodeoxycholate-lysophoshatidylethanolamide ameliorates mucosal inflammation in a genetic mouse model of ulcerative colitis
Stremmel W., Staffer S., Stuhrmann N., Gauss A., Burger N., Hornuss D.
University Hospital of Heidelberg, Internal Medicine IV, Dept. of Gastroenterology, Heidelberg, Germany
The mucosal attack by commensal microbiota is one component for induction of inflammatory episodes in ulcerative colitis (UC). Previously we could show that in UC the mucus layer is intrinsically devoid of phosphatidylcholine (PC) resulting in low hydrophobicity which facilitates bacterial invasion. Ectophospholipase carrying bacterial strains are most likely candidates to break the PC mucus barrier.
Our aim of this study was to evaluate the effect of phospholipase A2 (PLA2) inhibitors on prevention of inflammation in a genetic UC mouse model.
As PLA2 inhibitor we applied the bile acid-phospholpid conjugate ursodeoxycholate-lysophosphatidylethanolamide (UDCA-LPE). The tamoxifen-sensitive, intestinal specific kindlin 2 knockout mouse was used as a genetic model for UC. During 3 days of i.p. tamoxifen application to induce the UC phenotype, the control and experimental group were orally gavaged and a 100 μl bolus of 5% Tween80 or 100 mM UDCA-LPE in Tween80 was applied, respectively. At the 4th day the animals were sacrificed and analyzed in regard to the degree of mucosal inflammation as well as the change of colonic microbiota.
Luminal UDCA-LPE reduced the PLA2 activity in stool by 36±8%. Concominantly no inflammatory phenotype was observed when compared to kindlin 2(–/–) mice not treated with UDCA-LPE. The improvement was documented in regard to calprotectin in stool levels, endoscopic as well as histologic features. The pattern of colonic microbiota distribution obtained in the UC phenotype mice was reversed by UDCA-LPE to the control mice pattern.
The inhibition of the bacterial ectophospholipase A2 activity improves mucosal inflammation in a genetic mouse model of UC. It is assumed that the remaining mucus PC shield is better preserved when luminal PLA2 is suppressed.