Title : L. reuteri ZJ617 inhibits inflammatory and autophagy signaling pathways in gut-liver axis in piglet induced by lipopolysaccharide
Abstract:
Our previous study has isolated a probiotic strain Lactobacillus reuteri ZJ617 (ZJ617) from pig intestine with high adhesive ability and showed inhibition ability against pathogens potentially via S-layer proteins both in vitro and in mice study. In this study, the protective effects of ZJ617 on intestinal and liver injury and the underlying mechanisms in modulating inflammatory, autophagy, and apoptosis signaling pathways in a piglet challenged with lipopolysaccharide (LPS) were investigated. A total of 18 Duroc × Landrace × Large White piglets were assigned to 3 groups (n = 6/group), including control (CON), LPS, and ZJ617 + LPS group. The CON and LPS group received oral phosphate-buffered saline for 2 weeks and intraperitoneal injected (IP) with physiological saline or LPS, respectively. Piglets in ZJ617 + LPS group were orally inoculated with ZJ617 for 2 weeks before IP of LPS. Compared with CON, LPS stimulation significantly increased intestinal phosphorylated-p38 MAPK, phosphorylated-ERK and JNK protein levels and decreased IκBα protein expression, while LPS, TNF-α, and IL-6 levels in serum were increased (P < 0.05). Compared with CON, LPS stimulation significantly increased LC3, Atg5, and Beclin-1 protein expression (P < 0.05) but decreased ZO-1, claudin-3, and occludin protein expression (P < 0.05) and increased serum DAO and D-xylose levels, effects that were all countered by ZJ617 pretreatment. LPS induced significantly higher hepatic LC3, Atg5, Beclin-1, SOD-2, and Bax protein expression (P < 0.05) and lower hepatic total bile acid (TBA) levels (P < 0.05) compared with CON. ZJ617 pretreatment significantly decreased hepatic Beclin-1, SOD2, and Bax protein expression (P < 0.05) and showed a tendency to decrease hepatic TBA (P = 0.07) induced by LPS treatment. Pretreatment of ZJ617 before LPS injection induced the production of 5 significant metabolites in the intestinal contents: capric acid, isoleucine 1TMS, glycerol-1-phosphate byproduct, linoleic acid, alanine-alanine (P < 0.05). In conclusion, our results demonstrated that probiotic strain ZJ617 could alleviate LPS-induced intestinal tight junction protein destruction, and intestinal and hepatic inflammatory and autophagy signal activation in the piglets.
