Tianjin Key Laboratory of Animal Molecular Breeding and Biotechnology; Tianjin Engineering Research Center of Animal Healthy Farming; Institute of Animal Science and Veterinary, Tianjin Academy of Agricultural Sciences, Tianjin, China; State Key Laboratory of Animal Nutrition and Feeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, China; Tianfu Institute of Research and Innovation, Southwest University of Science and Technology, Chengdu, Sichuan, China.
Tianjin Key Laboratory of Animal Molecular Breeding and Biotechnology; Tianjin Engineering Research Center of Animal Healthy Farming; Institute of Animal Science and Veterinary, Tianjin Academy of Agricultural Sciences, Tianjin, China; College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
J Nutr Biochem. 2024 Nov;133:109719. doi: 10.1016/j.jnutbio.2024.109719. Epub 2024 Aug 3.
This study investigated the protective effect of dulcitol on LPS-induced intestinal injury in piglets and explored the underlying molecular mechanisms. A total of 108 piglets were divided into three groups: CON, LPS, and DUL. The CON and LPS groups were fed a basal diet, the DUL group was fed a diet supplementation with 500 mg/kg dulcitol. On day 29, 6 piglets in the LPS and DUL groups were injected with 100 μg/kg BW of LPS. At 4 h postchallenge, all pigs were slaughtered, and colonic samples were collected. Results showed that dulcitol supplementation boosted intestinal barrier function in LPS-challenged piglets by enhancing intestinal morphology and integrity, and increasing the gene expression of zonula occludens-1, claudin-1, and occludin in the colonic mucosa (P <0.05). Metabolomics showed DUL supplementation mainly increased (P <0.05) the metabolites related to steroid and vitamin metabolism (Cholesterol and Vitamin C). Proteomics showed that dulcitol supplementation altered the protein expression involved in maintaining barrier integrity (FN1, CADM1, and PARD3), inhibiting inflammatory response (SLP1, SFN, and IRF3), and apoptosis (including FAS, ING1, BTK, MTHFR, NOX, and P53BP2) in LPS-challenged piglets (P <0.05). Additionally, dulcitol addition also suppressed the TLR4/NF-κB signaling pathway and apoptosis in mRNA and protein levels. Dulcitol increased the abundance of short-chain fatty acid-producing bacteria (Lactobacillus, Blautia, and Faecalibacterium) at the genus level, but decreased the relative abundance of Proteobacteria at the phylum level and Pseudomonas and Delftia at the genus level in piglets (P<.05). In conclusion, these results suggested that the addition of dulcitol alleviated LPS-induced intestinal barrier injury in piglets, probably by maintaining its integrity, inhibiting the TLR4/NF-κB signaling pathways and apoptosis, and modulating the gut microbiota. Therefore, dulcitol can be considered a potential dietary additive for improving intestinal health in pig models.
本研究旨在探讨山梨醇对 LPS 诱导的仔猪肠道损伤的保护作用，并探讨其潜在的分子机制。将 108 头仔猪分为三组：CON、LPS 和 DUL。CON 和 LPS 组饲喂基础日粮，DUL 组在基础日粮中添加 500mg/kg 山梨醇。在第 29 天，LPS 和 DUL 组的 6 头仔猪注射 100μg/kgBW 的 LPS。攻毒后 4h，所有仔猪被屠宰，采集结肠样本。结果表明，山梨醇补充剂通过增强肠道形态和完整性，增加结肠黏膜中紧密连接蛋白-1、Claudin-1 和 Occludin 的基因表达，增强 LPS 攻毒仔猪的肠道屏障功能（P<0.05）。代谢组学显示，DUL 补充剂主要增加（P<0.05）与类固醇和维生素代谢相关的代谢物（胆固醇和维生素 C）。蛋白质组学显示，山梨醇补充剂改变了与维持屏障完整性（FN1、CADM1 和 PARD3）、抑制炎症反应（SLP1、SFN 和 IRF3）和凋亡（包括 FAS、ING1、BTK、MTHFR、NOX 和 P53BP2）相关的蛋白表达在 LPS 攻毒的仔猪中（P<0.05）。此外，山梨醇添加还抑制了 TLR4/NF-κB 信号通路和凋亡在 mRNA 和蛋白质水平上的表达。山梨醇增加了短链脂肪酸产生菌（乳杆菌、布劳特氏菌和粪肠球菌）的丰度，在属水平上，但降低了门水平上变形菌的相对丰度，在属水平上降低了假单胞菌和德氏菌的相对丰度在仔猪中（P<.05）。综上所述，这些结果表明，添加山梨醇可以缓解 LPS 诱导的仔猪肠道屏障损伤，可能通过维持其完整性、抑制 TLR4/NF-κB 信号通路和凋亡以及调节肠道微生物群来实现。因此，山梨醇可以被认为是一种改善猪模型肠道健康的潜在膳食添加剂。
