This study was to determine the effects of dietary emodin (ED) on the intestinal mucosal barrier, nuclear factor kappa-B (NF-κB) pathways, and gut microbial flora in lipopolysaccharide (LPS)-induced piglets. Twenty-four weaned piglets were chosen and 4 treatments were created by randomly distributing piglets into CON, ED, LPS, and ED_LPS groups. Experiments were done in a 2 × 2 factorial arrangement and maintained for 21 d. Dietary treatment (a basal diet or 300 mg/kg ED) and immunological challenge (LPS or sterile saline) were 2 major factors. Intraperitoneal injections of LPS or sterilized saline were given to piglets on d 21. Six hours after the LPS challenge, all piglets were euthanized for sample collection and analysis. The results showed that piglets of the ED_LPS group had higher (P < 0.05) villus height to crypt depth ratio (VCR), and lower (P < 0.05) plasma D-lactate and diamine oxidase (DAO) than the LPS group. Furthermore, ED inhibited (P < 0.05) the decrease of glutathione peroxidase (GSH-Px) and catalase (CAT) activities and increase of malonaldehyde level (P < 0.05) in jejunal mucosa induced by LPS. The mRNA levels of pro-inflammatory cytokine genes (IL-6, IL-1β, and TNF-α) were significantly reduced (P < 0.05), and the mRNA levels of antioxidant enzyme genes (GPX-1, SOD2 and CAT), as well as protein and mRNA levels of tight junction proteins (occludin, claudin-1, and ZO-1), were also significantly increased (P < 0.05) by ED addition in LPS-induced piglets. Meanwhile, ED supplementation significantly decreased the LPS-induced protein levels of cyclooxygenase-2 and phosphorylation levels of NF-κB p65 and IκBα in jejunal mucosa. Emodin had a significant effect on the composition of gut microbial flora at various taxonomic positions as indicated by 16S RNA sequencing. The acetic acid, isobutyric acid, valeric acid, and isovaleric acid concentrations in the cecum were also increased by ED addition in pigs (P < 0.05). Furthermore, the correlation analysis revealed that some intestinal microbiota had a potential relationship with jejunal VCR, plasma D-lactate and DAO, jejunal mucosa GSH-Px and CAT activity, and cecal short-chain fatty acid concentration. These data suggest that ED is effective in alleviating LPS-induced intestinal mucosal barrier injury by modulating gut microbiota in piglets.

本研究旨在确定日粮大黄素 (ED) 对脂多糖 (LPS) 诱导仔猪的肠粘膜屏障、核因子 kappa-B (NF-κB) 通路和肠道微生物菌群的影响。选择 24 头断奶仔猪，通过将仔猪随机分为 CON、ED、LPS 和 ED_LPS 组来创建 4 个处理。实验以 2 × 2 阶乘排列进行并维持 21 d。饮食治疗（基础饮食或 300 mg/kg ED）和免疫激发（LPS 或无菌盐水）是两个主要因素。第21天对仔猪进行腹腔注射LPS或无菌生理盐水。LPS攻击后六小时，对所有仔猪实施安乐死以进行样品收集和分析。结果表明 ED_LPS 组仔猪具有较高的 ( P < 0.05) 绒毛高度与隐窝深度比 (VCR)，且血浆 D-乳酸和二胺氧化酶 (DAO) 低于 ( P  < 0.05) LPS 组。此外，ED还抑制 LPS引起的空肠粘膜 谷胱甘肽过氧化物酶（GSH-Px）和过氧化氢酶（CAT）活性的降低（P < 0.05）以及丙二醛水平的升高（ P < 0.05）。促炎细胞因子基因（IL-6、IL-1β、 TNF -α） mRNA水平显着降低（P  < 0.05），抗氧化酶基因（GPX-1、SOD2、CAT）mRNA水平显着降低（P < 0.05）。以及紧密连接蛋白（occludin、claudin-1 和 在 LPS 诱导的仔猪中，通过添加 ED，ZO-1也显着增加（P < 0.05）。同时，补充ED显着降低了LPS诱导的空肠粘膜中环氧合酶2的蛋白水平以及NF-κB p65和IκBα的磷酸化水平。16S RNA 测序表明，大黄素对不同分类位置的肠道微生物菌群组成具有显着影响。添加 ED 也增加了猪盲肠中乙酸、异丁酸、戊酸和异戊酸的浓度（P < 0.05）。此外，相关性分析显示，一些肠道微生物群与空肠VCR、血浆D-乳酸和DAO、空肠粘膜GSH-Px和CAT活性以及盲肠短链脂肪酸浓度存在潜在关系。这些数据表明，ED 通过调节仔猪肠道微生物群，有效减轻 LPS 诱导的肠粘膜屏障损伤。