Abstract
Background Infection with pathogenic bacteria during nonantibiotic breeding is one of the main causes of animal intestinal diseases.Oleanolic acid(OA)is a pentacyclic triterpene that is ubiquitous in plants.Our previous work dem-onstrated the protective effect of OA on intestinal health,but the underlying molecular mechanisms remain unclear.This study investigated whether dietary supplementation with OA can prevent diarrhea and intestinal immune dysregulation caused by enterotoxigenic Escherichia coli(ETEC)in piglets.The key molecular role of bile acid receptor signaling in this process has also been explored.Results Our results demonstrated that OA supplementation alleviated the disturbance of bile acid metabolism in ETEC-infected piglets(P＜0.05).OA supplementation stabilized the composition of the bile acid pool in piglets by regulating the enterohepatic circulation of bile acids and significantly increased the contents of UDCA and CDCA in the ileum and cecum(P＜0.05).This may also explain why OA can maintain the stability of the intestinal micro-biota structure in ETEC-challenged piglets.In addition,as a natural ligand of bile acid receptors,OA can reduce the severity of intestinal inflammation and enhance the strength of intestinal epithelial cell antimicrobial programs through the bile acid receptorsTGR5 and FXR(P＜0.05).Specifically,OA inhibited NF-κB-mediated intestinal inflam-mation by directly activating TGR5 and its downstream cAMP-PKA-CREB signaling pathway(P＜0.05).Furthermore,OA enhanced CDCA-mediated MEK-ERK signaling in intestinal epithelial cells by upregulating the expression of FXR(P＜0.05),thereby upregulating the expression of endogenous defense molecules in intestinal epithelial cells.Conclusions In conclusion,our findings suggest that OA-mediated regulation of bile acid metabolism plays an important role in the innate immune response,which provides a new diet-based intervention for intestinal dis-eases caused by pathogenic bacterial infections in piglets.
基金项目
National Natural Science Foundation of China(31972580)
National Natural Science Foundation of China(U21A20252)
China Agriculture Research System(CARS-35)
Science Fund for Distinguished Young Scholars of Heilongjiang Province(JQ2022C002)
Support Project of Young Leading Talents of Northeast Agricultural University(NEAU2023QNLJ-017)
万方数据