Abstract：
The intestine defends against pathogenic microbial invasion via the secretion of host defense peptides (HDPs). Nutritional immunomodulation can stimulate the expression of endogenous HDPs and enhance the body\'s immune defense, representing a novel non-antibiotic strategy for disease prevention. The project aims to explore the regulatory mechanism of protegrin-1 (PG-1) expression using sodium phenylbutyrate (PBA) by omics sequencing technology and further investigate the role of key regulatory genes on intestinal health. The results showed that PBA promoted PG-1 expression in intestinal epithelial cells based on cell density through epidermal growth factor receptor (EGFR) and G protein-coupled receptor (GPR43). Transcriptome sequencing and microRNA sequencing revealed that C-X-C motif chemokine receptor 2 (CXCR2) exhibited interactions with PG-1. Pre-treatment cells with a CXCR2 inhibitor (SB225002) effectively suppressed the induction of PG-1 by PBA. Furthermore, SB225002 significantly suppressed the gene expression of HDPs in the jejunum of mice without influencing on the morphology, number of goblet cells, and proliferation of the intestine. CXCR2 inhibition significantly reduced the expression of HDPs during E. coli infection, and resulted in the edema of jejunal epithelial cells. The 16S rDNA analysis of cecal contents showed that the E. coli and SB225002 treatments changed gut microbiota diversity and composition at different taxonomic levels. Correlation analysis suggested a potential regulatory relationship between gut microbiota and HDPs. To that end, a gene involved in the HDP expression, CXCR2, has been identified in the study, which contributes to improving intestinal immune function. PBA may be used as a functional additive to regulate intestinal mucosal function, thereby enhancing the health of the intestinal and host.
摘要：
肠道通过分泌宿主防御肽（HDP）来防御病原微生物入侵。营养免疫调节可以刺激内源性HDPs的表达，增强机体的免疫防御能力，代表了一种新型的非抗生素疾病预防策略。本项目旨在通过组学测序技术探讨苯丁酸钠(PBA)对proteogrin-1(PG-1)表达的调控机制,并进一步探讨关键调控基因在肠道健康中的作用。结果表明，PBA通过表皮生长因子受体（EGFR）和G蛋白偶联受体（GPR43）促进基于细胞密度的肠上皮细胞中PG-1的表达。转录组测序和microRNA测序显示，C-X-C基序趋化因子受体2（CXCR2）与PG-1相互作用。用CXCR2抑制剂(SB225002)预处理细胞有效地抑制PBA对PG-1的诱导。此外，SB225002显著抑制小鼠空肠内HDPs的基因表达,而不影响其形态学,杯状细胞的数量，和肠道的增殖。CXCR2抑制在大肠杆菌感染期间显著降低HDPs的表达,并导致空肠上皮细胞水肿。盲肠内容物的16SrDNA分析表明，大肠杆菌和SB225002处理在不同的分类水平上改变了肠道微生物群的多样性和组成。相关分析表明，肠道菌群与HDPs之间存在潜在的调节关系。为此,参与HDP表达的基因，CXCR2，已在研究中确定，这有助于提高肠道免疫功能。PBA可用作调节肠粘膜功能的功能性添加剂。从而增强肠道和宿主的健康。
