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 previo...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 demonstrated 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 microbiota 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 receptors TGR5 and FXR(P<0.05).Specifically,OA inhibited NF-κB-mediated intestinal inflammation by directly activating TGR5 and its downstream c AMP-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 diseases caused by pathogenic bacterial infections in piglets.展开更多
Disturbance of the inflammatory response in the gut is important in several clinical diseases ranging from inflmmatory bowel disease to postoperative ileus. Several feedback mechanisms exist that control the inflammat...Disturbance of the inflammatory response in the gut is important in several clinical diseases ranging from inflmmatory bowel disease to postoperative ileus. Several feedback mechanisms exist that control the inflammatory cascade and avoid collateral damage. In the gast rointestinal tract, it is of particular importance tocontrol the immune response to maintain the balance that allows dietary up take and utilization of nutrientson one hand, while preventing invasion of bacteria and toxins on the other hand. The process of digestion and absorption of nutrients requires a relative hyporesponsiveness of the immune cells in the gut to luminacontents which is not yet fully understood. Recentlythe autonomic nervous system has been identifi ed asan important pathway to control local and systemic inflammation and gut barrier integrity. Activation of thepathway is possible via electrical or via pharm acological interventions, but is also achieved in a physiologicamanner by ingestion of dietary lipids. Administration of dietary lipids has been shown to be very effectivein reducing the inflammatory cascade and maintaining intestinal barrier integrity in several experimental studies. This beneficial effect of nutrition on the inflammatory response and intestinal barrier integrity opens new therapeutic opportunities for treatment of certain gastrointestinal disorders. Furthermore, this neural feedback mechanism provides more insight in the relative hyporesponsiveness of the immune cells in the gut. Here, we will discuss the regulatory function of the autonomic nervous system on the inflammatory response and gut barrier function and the potential benefit in a clinical setting.展开更多
基金financially supported by the National Natural Science Foundation of China(Grant No.31972580 and U21A20252)the China Agriculture Research System(CARS-35)+1 种基金the Science Fund for Distinguished Young Scholars of Heilongjiang Province(JQ2022C002)the Support Project of Young Leading Talents of Northeast Agricultural University(NEAU2023QNLJ-017)。
文摘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 demonstrated 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 microbiota 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 receptors TGR5 and FXR(P<0.05).Specifically,OA inhibited NF-κB-mediated intestinal inflammation by directly activating TGR5 and its downstream c AMP-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 diseases caused by pathogenic bacterial infections in piglets.
文摘Disturbance of the inflammatory response in the gut is important in several clinical diseases ranging from inflmmatory bowel disease to postoperative ileus. Several feedback mechanisms exist that control the inflammatory cascade and avoid collateral damage. In the gast rointestinal tract, it is of particular importance tocontrol the immune response to maintain the balance that allows dietary up take and utilization of nutrientson one hand, while preventing invasion of bacteria and toxins on the other hand. The process of digestion and absorption of nutrients requires a relative hyporesponsiveness of the immune cells in the gut to luminacontents which is not yet fully understood. Recentlythe autonomic nervous system has been identifi ed asan important pathway to control local and systemic inflammation and gut barrier integrity. Activation of thepathway is possible via electrical or via pharm acological interventions, but is also achieved in a physiologicamanner by ingestion of dietary lipids. Administration of dietary lipids has been shown to be very effectivein reducing the inflammatory cascade and maintaining intestinal barrier integrity in several experimental studies. This beneficial effect of nutrition on the inflammatory response and intestinal barrier integrity opens new therapeutic opportunities for treatment of certain gastrointestinal disorders. Furthermore, this neural feedback mechanism provides more insight in the relative hyporesponsiveness of the immune cells in the gut. Here, we will discuss the regulatory function of the autonomic nervous system on the inflammatory response and gut barrier function and the potential benefit in a clinical setting.
