1205. Protectin D1 Induced by Clostridium butyricum MIYAIRI 588 Has an Anti-inflammatory Effects on Antibiotic-induced Intestinal Disorder

Abstract

BackgroundThe administration of Clostridium butyricum MIYAIRI 588 (CBM 588) upregulates protectin D1,the anti-inflammatory lipid metabolites, in colon tissue under the antibiotic therapy. However, how CBM 588 induces protectin D1 nor whether the metabolite has anti-inflammatory effects on antibiotic-induced enteritis are unclear. Therefore, we evaluated the effect of CBM 588 on lipid metabolism and protectin D1 on immunological functions in colon tissue.MethodsMice were divided into five groups and clindamycin (CLDM), CBM 588 and/or protectin D1 were administered for 4 days (1. Control, 2. CLDM group, 3. CBM 588 group, 4. CLDM plus CBM 588 group and 5. CLDM plus protectin D1 group). After 4 days of administration, mice were reared for an additional 4 days. On day 8, colon tissues were removed to measure lipid metabolites with LC-MS/MS. Also, cytokines, lipid metabolism relative genes, enzymes were measured with qRT-PCR and ELISA.ResultsIn the CBM588 treatment group, protectin D1, α-linolenic acid, eicosapentaenoic acid (EPA) and autoxidation product of DHA (docosahexaenoic acid) were significantly increased, compared with CLDM group and control. At the same time, genes expression levels of polyunsaturated fatty acids (PUFAs) receptors, G-protein coupled receptor 120 (GPR120) and a DHA to protectin D1 metabolizing enzyme 15- lipoxygenase (LOX) in colon tissue increased. Il-4 produced by Th2 cells, also increased in CBM588 treated groups even under CLDM co-administration. In addition, similar to CBM 588, protectin D1 administration suppressed mice’s weight loss due to gut inflammation, decreased inflammatory cytokines, while anti-inflammatory cytokine IL-10 and TGF-β1 increased.PUFAs metabolism cascade induced by CBM 588. Lipid metabolism relative genes, pro/anti-inflammatory cytokines and body weight. ConclusionOur data suggested that CBM 588 stimulated PUFAs metabolism in the intestinal tract, and that PUFAs were signaled to Th2 cells as a ligand of GPR120. It was speculated that the stimulated Th2 cells produced IL4 and activated 15-LOX, resulting in the induction of protectin D1. Also, it became clear that protectin D1 induced anti-inflammatory cytokines in controlling antibiotic-induced gut inflammation. We provide as a new insight that lipid metabolism induction for the treatment of gut inflammatory diseases with CBM 588.Anti-inflammatory pathway of protectin D1 induced by CBM 588. Disclosures Hiroshige Mikamo, M.D, Ph.D, Astellas Pharma Inc. (Grant/Research Support, Speaker’s Bureau)MSD Japan (Grant/Research Support, Speaker’s Bureau)Pfizer Japan Inc. (Grant/Research Support)Sumitomo Dainippon Pharma Co., Ltd (Grant/Research Support, Speaker’s Bureau)