L. reuteri ZJ617 inhibits inflammatory and autophagy signaling pathways in gut-liver axis in piglet induced by lipopolysaccharide

Background This study investigated the protective effects of L. reuteri 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). Methods Duroc × Landrace × Large White piglets were assigned to 3 groups ( n = 6/group): control (CON) and LPS groups received oral phosphate-buffered saline for 2 weeks before intraperitoneal injection (i.p.) of physiological saline or LPS (25 μg/kg body weight), respectively, while the ZJ617 + LPS group was orally inoculated with ZJ617 for 2 weeks before i.p. of LPS. Piglets were sacrificed 4 h after LPS injection to determine intestinal integrity, serum biochemical parameters, inflammatory signaling involved in molecular and liver injury pathways. Results Compared with controls, LPS stimulation significantly increased intestinal phosphorylated-p38 MAPK, phosphorylated-ERK and JNK protein levels and decreased IκBα protein expression, while serum LPS, TNF-α, and IL-6 concentrations ( P < 0.05) increased. ZJ617 pretreatment significantly countered the effects induced by LPS alone, with the exception of p-JNK protein levels. Compared with controls, 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 controls. ZJ617 pretreatment significantly decreased hepatic Beclin-1, SOD2, and Bax protein expression ( P < 0.05) and showed a tendency to decrease hepatic TBA ( P = 0.0743) 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). Conclusions These results demonstrated that ZJ617 pretreatment alleviated LPS-induced intestinal tight junction protein destruction, and intestinal and hepatic inflammatory and autophagy signal activation in the piglets.