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 for2 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-6concentrations(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 5significant 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.