PDF(Pubmed)
Abstract：
Intrauterine growth restriction (IUGR) pigs are characterized by long-term growth failure, metabolic disorders, and intestinal microbiota imbalance. The characteristics of the negative effects of IUGR at different growth stages of pigs are still unclear. Therefore, this study explored through multi-omics analyses whether the IUGR damages the intestinal barrier function and alters the colonization and metabolic profiles of the colonic microbiota in growing-finishing pigs. Seventy-two piglets (36 IUGR and 36 NBW) were allocated for this trial to analyze physiological and plasma biochemical parameters, as well as oxidative damage and inflammatory response in the colon. Moreover, the colonic microbiota communities and metabolome were examined using 16s rRNA sequencing and metabolomics technologies to reveal the intestinal characteristics of IUGR pigs at different growth stages (25, 50, and 100 kg). IUGR altered the concentrations of plasma glucose, total protein, triglycerides, and cholesterol. Colonic tight junction proteins were markedly inhibited by IUGR. IUGR decreased plasma T-AOC, SOD, and GSH levels and colonic SOD-1, SOD-2, and GPX-4 expressions by restraining the Nrf2/Keap1 signaling pathway. Moreover, IUGR increased colonic IL-1β and TNF-α levels while reducing IL-10, possibly through activating the TLR4-NF-κB/ERK pathway. Notably, IUGR pigs had lower colonic Streptococcus abundance and Firmicutes-to-Bacteroidetes ratio at the 25 kg BW stage while having higher Firmicutes abundance at the 100 kg BW stage; moreover, IUGR pigs had lower SCFA concentrations. Metabolomics analysis showed that IUGR increased colonic lipids and lipid-like molecules, organic acids and derivatives, and organoheterocyclic compounds concentrations and enriched three differential metabolic pathways, including linoleic acid, sphingolipid, and purine metabolisms throughout the trial. Collectively, IUGR altered the nutrient metabolism, redox status, and colonic microbiota community and metabolite profiles of pigs and continued to disrupt colonic barrier function by reducing antioxidant capacity via the Nrf2/Keap1 pathway and activating inflammation via the TLR4-NF-κB/ERK pathway during the growing-finishing stage. Moreover, colonic Firmicutes and Streptococcus could be potential regulatory targets for modulating the metabolism and health of IUGR pigs.
摘要：
宫内生长受限（IUGR）猪的特征是长期生长障碍，代谢紊乱，和肠道微生物群失衡。IUGR在猪不同生长阶段的负效应特征尚不清楚。因此,这项研究通过多组学分析探讨了IUGR是否会损害肠道屏障功能并改变生长育肥猪结肠微生物群的定植和代谢谱。本试验分配72只仔猪(36只IUGR和36只NBW)进行生理和血浆生化指标分析,以及结肠的氧化损伤和炎症反应。此外，我们使用16srRNA测序和代谢组学技术检测了结肠微生物群落和代谢组,以揭示不同生长阶段(25,50和100kg)IUGR猪的肠道特征.IUGR改变了血浆葡萄糖的浓度，总蛋白质，甘油三酯，和胆固醇。结肠紧密连接蛋白被IUGR显著抑制。IUGR降低血浆T-AOC，SOD,GSH水平和结肠SOD-1、SOD-2和GPX-4的表达通过抑制Nrf2/Keap1信号通路。此外，IUGR可能通过激活TLR4-NF-κB/ERK途径增加结肠IL-1β和TNF-α水平，同时降低IL-10。值得注意的是,IUGR猪在25kgBW阶段具有较低的结肠链球菌丰度和厚壁菌与拟杆菌比率，而在100kgBW阶段具有较高的厚壁菌丰度；此外，IUGR猪具有较低的SCFA浓度。代谢组学分析显示IUGR增加结肠脂质和类脂分子,有机酸及其衍生物，和有机杂环化合物的浓度和丰富的三个差异代谢途径，包括亚油酸,鞘脂，以及整个试验中的嘌呤代谢。总的来说，IUGR改变了营养代谢，氧化还原状态，和猪的结肠微生物群落和代谢物谱，并在生长结束阶段通过Nrf2/Keap1途径降低抗氧化能力并通过TLR4-NF-κB/ERK途径激活炎症，继续破坏结肠屏障功能。此外，结肠Firmicutes和链球菌可能是调节IUGR猪代谢和健康的潜在调节靶标。
