Abstract
Metabolites are thought as the end products in cellular regulatory processes and their levels show the strongest relationships with the phenotype. Previously, we showed that the administration of Clostridium butyricum MIYAIRI 588 (CBM 588) upregulated protectin D1, an anti-inflammatory lipid metabolite, in colon tissue under antibiotic therapy. However, how CBM 588 induces protectin D1 expression and whether the metabolite has anti-inflammatory effects on antibiotic-induced inflammation are unclear. Therefore, here, we evaluated the effect of CBM 588 on lipid metabolism and protectin D1 in gut protection from antibiotic-induced intestinal disorders. In the CBM 588 treatment group, expression levels of genes encoding lipid receptors related to the conversion of DHA to protectin D1, such as polyunsaturated fatty acid (PUFA) receptors, G-protein coupled receptor 120 (GPR120), and 15-lipoxygenase (LOX), were increased in colon tissue. CD4+ cells producing interleukin (IL)-4, the main component of T helper type 2 (Th2) cells that can activate 15-LOX, also increased in CBM 588-treated groups even after clindamycin co-administration. In addition, similar to CBM 588, exogenously administered protectin D1 reduced inflammatory cytokines, while IL-10 and TGF-β1, works as anti-inflammatory cytokines, were increased. Our data revealed that CBM 588 activated 15-LOX to enhance protectin D1 production by increasing IL-4-producing CD4+ cell population in the intestinal tract. Additionally, CBM 588-induced protectin D1 clearly upregulated IL-10-producing CD4+ cells to control antibiotic-induced gut inflammation. We provide new insights into CBM 588-mediated lipid metabolism induction for the treatment of gut inflammatory diseases.
Highlights
Metabolites are the end products of cellular metabolism
The gene expression level related to fatty acid metabolism in colon tissue was evaluated by Real-Time Polymerase Chain Reaction (RT-PCR), and we found that Clostridium butyricum MIYAIRI 588 (CBM 588) administration increased several orphan G-protein coupled receptor (GPR) RNA expression levels in colon tissue, such as of GPR41, GPR43, GPR84, and G-protein coupled receptor 120 (GPR120) (Figure 4A)
In the in vivo colitis model, arachidonic acid (AA) release and subsequent prostanoids, such as PGE1, PGE2, and PGF1 were significantly increased in the colonic mucosa (Hoang et al, 2007)
Summary
Metabolites are the end products of cellular metabolism. They have a strong correlation with phenotype, and levels of metabolites provide more comprehensive understanding of biological system’s response to genetic changes and environmental changes. Gobbetti et al (2017) revealed that bioactive lipid mediators of docosapentaenoic acid (DPA) and eicosapentaenoic acid (EPA) metabolites have the functional roles in intestinal inflammation. Metabolites are the end products of cellular metabolism They have a strong correlation with phenotype, and levels of metabolites provide more comprehensive understanding of biological system’s response to genetic changes and environmental changes. Gobbetti et al (2017) revealed that bioactive lipid mediators of docosapentaenoic acid (DPA) and eicosapentaenoic acid (EPA) metabolites have the functional roles in intestinal inflammation. These metabolites administrations attenuate dextran sulfate sodium (DSS)-induced colitis in mice through decreased leukocyte—endothelial interaction and reduced granulocyte trafficking. The effects of CBM 588 administration on lipid metabolic changes and whether these alterations have a crucial role in the anti-inflammatory effects remain unclear
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