Clostridium butyricum MIYAIRI 588-Induced Protectin D1 Has an Anti-inflammatory Effect on Antibiotic-Induced Intestinal Disorder

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 588treated 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.

Butyrate-producing human gut symbiont, Clostridium butyricum, and its role in health and disease

“…44 Finally, Hagihara and colleagues have also reported that the protective effect of C. butyricum on the intestinal barrier was associated with host metabolic alterations that lead to attenuation of antibioticinduced gut inflammation. 15,45 C. butyricum promoted the production of anti-inflammatory lipid metabolites such as palmitoleic acids, prostaglandin metabolites, and specialized pro-resolving mediators in mouse colonic tissues. Such lipid metabolites, especially protectin D1, 46 contribute to the promotion of anti-inflammatory IL-10 secreting T-cells in the colon.…”

Clostridium butyricum MIYAIRI 588 Modifies Bacterial Composition under Antibiotic-Induced Dysbiosis for the Activation of Interactions via Lipid Metabolism between the Gut Microbiome and the Host

“…Moreover, not only gastrointestinal mucosa-related diseases but also insulin resistance, obesity, and non-alcoholic fatty liver disease (NASH) have revealed that gut dysbiosis is one of the causes of abnormal host metabolism due to a decrease in beneficial bacteria [6][7][8]. Alterations in gut immune cell constitution and lipid metabolism are related to antibioticinduced dysbiosis and exacerbate gut inflammation, mucosa, and epithelial damage in the colon of mice [9,10]. Currently, to develop a treatment method for dysbiosis-induced gut Biomedicines 2021, 9, 1065 2 of 19 inflammation, research on live biotherapeutic products (LBPs) has been enthusiastically carried out [11,12].…”

New Perspectives in the Study of Intestinal Inflammation: Focus on the Resolution of Inflammation

“…PD1 treatment to mice that were subjected to DSS-induced colitis, together with an eosinophil depletion, prevented colon shortening and neutrophil infiltration, improved colonic histology scores, and reduced the expression of pro-inflammatory and chemotactic factors, such as TNF-α, IL-1β, CXCL1, and CXCL2 [ 71 ]. Similarly, PD1 exogenous administration reduced the severity of antibiotic-induced colon inflammation [ 72 ]. PD1 treatment also caused a prevention of shortening of the colon length, as well as an amelioration in the epithelial damage and histologic inflammation scores, as observed in the DSS colitis model [ 72 ].…”

“…Similarly, PD1 exogenous administration reduced the severity of antibiotic-induced colon inflammation [ 72 ]. PD1 treatment also caused a prevention of shortening of the colon length, as well as an amelioration in the epithelial damage and histologic inflammation scores, as observed in the DSS colitis model [ 72 ]. Finally, a congenerous of protectins family produced by the metabolism of n-3 docosapentaenoic acid (n-3 DPA), namely PD1n-3 DPA, was reported to protect mice from inflammation during the course of acute DSS-induced colitis [ 20 ].…”