Clostridium butyricum MIYAIRI 588-Induced Protectin D1 Has an Anti-inflammatory Effect on Antibiotic-Induced Intestinal Disorder
Tadashi Ariyoshi, Mao Hagihara, Shuhei Eguchi, Fukuda Aiki, Kenta Iwasaki, Kentaro Oka, Motomichi Takahashi, Yuka Yamagishi, Hiroshige Mikamo
Abstract
Metabolites are the end products of cellular regulatory processes and have a strong correlation to phenotype. In our previous study, the administration of Clostridium butyricum MIYAIRI 588 (CBM 588) upregulated protectin D1, is one of the anti-inflammatory lipid metabolites, in colon tissue under the antibiotic therapy. However, how CBM588 induces protectin D1 nor whether the metabolite has anti-inflammatory effects on antibiotic-induced inflammation is unclear. Therefore, we evaluated the impacts of CBM588 on lipid metabolism and protectin D1 on gut protection from antibiotic-induced intestinal disorder. In the CBM 588 treatment group, gene expression levels of lipid receptor, related to DHA metabolism to protectin D1, such as polyunsaturated fatty acids (PUFAs) receptors, G-protein coupled receptor 120 (GPR120) and 15- lipoxygenase (LOX), were increased in colon tissue. IL-4 producing CD4+ cells, is main component of Th2 cells and can activate 15-LOX, also increased in CBM 588 treated groups even under CLDM co-administration. In addition, similar to CBM 588, protectin D1 exogenous administration reduced inflammatory cytokines, while anti-inflammatory cytokine, such as IL-10 and TGF-β1, were increased. Our data revealed that CBM 588 activate 15-LOX to enhance protectin D1 production through IL-4 producing CD4+ cells upregulation in the intestinal tract. Additionally, it became clear that CBM 588 induced-protectin D1 upregulated IL-10 producing CD4+ cells to control antibiotic-induced gut inflammation. We provide as a new insight that lipid metabolism induction for the treatment of gut inflammatory diseases with CBM 588.