MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, China.
MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu, China.
Vet Microbiol. 2024 Aug;295:110152. doi: 10.1016/j.vetmic.2024.110152. Epub 2024 Jun 17.
The intestinal barrier of newborn piglets is vulnerable and underdeveloped, making them susceptible to enteric virus infections. Benzoic acid (BA), employed as a growth promoter, exhibits the potential to enhance the gut health of piglets by modulating intestinal morphometry and tight junction dynamics. However, the extent to which BA regulates the intestinal mucus barrier through its impact on stem cells remains inadequately elucidated. Therefore, this study was conducted to investigate the effects of BA on the intestinal barrier and the differentiation of intestinal stem cells, employing in vivo piglet and in vitro intestinal organoid models. Our investigation revealed a significant increase in the number of goblet cells within the small intestine, as well as the strengthening of the mucus barrier in vivo following oral treatment with BA, providing partial protection against PEDV infection in piglets. Additionally, in vitro cultivation of enteroids with BA led to a notable increase in the number of MUC2 GCs, indicating the promotion of GC differentiation by BA. Furthermore, transcriptome analysis revealed an upregulation of the number of GCs and the expression of cell vesicle transport-related genes during BA stimulation, accompanied by the downregulation of the Wnt and Notch signaling pathways. Mechanistically, MCT1 facilitated the transport of BA, subsequently activating the MAPK pathway to mediate GC differentiation. Overall, this study highlights a novel function for BA as a feed additive in enhancing the intestinal mucus barrier by promoting intestinal GC differentiation, and further prevents viral infection in piglets.
新生仔猪的肠道屏障脆弱且发育不全，使它们容易受到肠道病毒感染。苯甲酸（BA）作为一种生长促进剂，通过调节肠道形态和紧密连接动力学，具有增强仔猪肠道健康的潜力。然而，BA 通过影响干细胞来调节肠道粘液屏障的程度仍未得到充分阐明。因此，本研究采用体内仔猪和体外肠类器官模型，研究 BA 对肠道屏障和肠干细胞分化的影响。我们的研究表明，BA 经口服处理后，仔猪体内小肠内杯状细胞数量显著增加，粘液屏障增强，对 PEDV 感染提供部分保护。此外，用 BA 体外培养肠类器官导致 MUC2 GCs 的数量显著增加，表明 BA 促进 GC 分化。此外，转录组分析显示，BA 刺激时 GC 数量增加，与细胞囊泡转运相关基因的表达上调，同时 Wnt 和 Notch 信号通路下调。在机制上，MCT1 促进 BA 的转运，随后激活 MAPK 途径介导 GC 分化。总的来说，这项研究强调了 BA 作为一种饲料添加剂的新功能，通过促进肠道 GC 分化来增强肠道粘液屏障，并进一步防止仔猪的病毒感染。
