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). 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. 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). 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.

中文翻译：

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罗伊氏乳杆菌ZJ617抑制脂多糖诱导仔猪肠肝轴炎症和自噬信号通路

本研究调查了罗伊氏乳杆菌 ZJ617 对肠道和肝损伤的保护作用，以及在脂多糖 (LPS) 攻击的仔猪中调节炎症、自噬和凋亡信号通路的潜在机制。Duroc × Landrace × Large White 仔猪分为 3 组（n = 6/组）：对照组（CON）和 LPS 组在腹腔注射（ip）生理盐水或 LPS（25 μg）前接受口服磷酸盐缓冲盐水 2 周。 /kg 体重），而 ZJ617 + LPS 组在 LPS 腹腔注射前口服接种 ZJ617 2 周。LPS 注射后 4 小时处死仔猪以确定肠道完整性、血清生化参数、参与分子和肝损伤途径的炎症信号。与对照相比，LPS 刺激显着增加肠道磷酸化-p38 MAPK、磷酸化-ERK 和 JNK 蛋白水平并降低 IκBα 蛋白表达，而血清 LPS、TNF-α 和 IL-6 浓度增加（P < 0.05）。ZJ617 预处理显着抵消了单独由 LPS 诱导的影响，但 p-JNK 蛋白水平除外。与对照组相比，LPS 刺激显着增加 LC3、Atg5 和 Beclin-1 蛋白表达（P < 0.05），但降低 ZO-1、claudin-3 和 occludin 蛋白表达（P < 0.05）并增加血清 DAO 和 D-木糖ZJ617 预处理所抵消的影响。与对照组相比，LPS 诱导显着更高的肝脏 LC3、Atg5、Beclin-1、SOD-2 和 Bax 蛋白表达（P < 0.05）和更低的肝脏总胆汁酸（TBA）水平（P < 0.05）。ZJ617 预处理显着降低肝脏 Beclin-1、SOD2 和 Bax 蛋白表达（P < 0.05），并显示出降低 LPS 诱导的肝脏 TBA（P = 0.0743）的趋势。在 LPS 注射前预处理 ZJ617 诱导肠内容物中产生 5 种显着代谢物：癸酸、异亮氨酸 1TMS、甘油-1-磷酸副产物、亚油酸、丙氨酸-丙氨酸（P < 0.05）。这些结果表明，ZJ617 预处理减轻了 LPS 诱导的小猪肠道紧密连接蛋白破坏，以及肠道和肝脏炎症和自噬信号的激活。在 LPS 注射前预处理 ZJ617 诱导肠内容物中产生 5 种显着代谢物：癸酸、异亮氨酸 1TMS、甘油-1-磷酸副产物、亚油酸、丙氨酸-丙氨酸（P < 0.05）。这些结果表明，ZJ617 预处理减轻了 LPS 诱导的小猪肠道紧密连接蛋白破坏，以及肠道和肝脏炎症和自噬信号的激活。在 LPS 注射前预处理 ZJ617 诱导肠内容物中产生 5 种显着代谢物：癸酸、异亮氨酸 1TMS、甘油-1-磷酸副产物、亚油酸、丙氨酸-丙氨酸（P < 0.05）。这些结果表明，ZJ617 预处理减轻了 LPS 诱导的小猪肠道紧密连接蛋白破坏，以及肠道和肝脏炎症和自噬信号的激活。