Project description:Opioid analgesics are frequently prescribed in the United States and worldwide. However, serious side effects such as addiction, immunosuppression and gastrointestinal symptoms limit long term use. In the current study using a chronic morphine-murine model a longitudinal approach was undertaken to investigate the role of morphine modulation of gut microbiome as a mechanism contributing to the negative consequences associated with opioids use. The results revealed a significant shift in the gut microbiome and metabolome within 24 hours following morphine treatment when compared to placebo. Morphine induced gut microbial dysbiosis exhibited distinct characteristic signatures profiles including significant increase in communities associated with pathogenic function, decrease in communities associated with stress tolerance. Collectively, these results reveal opioids-induced distinct alteration of gut microbiome, may contribute to opioids-induced pathogenesis. Therapeutics directed at these targets may prolong the efficacy long term opioid use with fewer side effects.
Project description:91 preterm infant gut metaproteomes measured in technical duplicate using an eleven salt pulse 2D-LC-MS/MS method. Samples represent 17 preterm infants over the first several weeks of life, of which 6 preterm infants eventually developed necrotizing enterocolitis.
Project description:Necrotizing enterocolitis (NEC) is the most common and lethal gastrointestinal disease affecting preterm infants. NEC develops suddenly and is characterized by gut barrier destruction, an inflammatory response, intestinal necrosis and multi-system organ failure. There is currently no method for early NEC detection, and the pathogenesis of NEC remains unclear.
2022-09-13 | GSE212913 | GEO
Project description:Gut virome in necrotizing enterocolitis
Project description:Necrotizing enterocolitis (NEC) is a prevalent pediatric emergency characterized by the sudden onset of intestinal ischemia and necrosis resulting from hyperinflammation.The interactions between the bile acid receptor FXR with gut microbiota and mucosal immunity in early postnatal life, and its exact role in the pathogenesis of NEC, are unknown.Here we analyze the role of FXR in IECs under NEC.
Project description:Necrotizing enterocolitis (NEC) is a prevalent pediatric emergency characterized by the sudden onset of intestinal ischemia and necrosis resulting from hyperinflammation.The interactions between the bile acid receptor FXR with gut microbiota and mucosal immunity in early postnatal life, and its exact role in the pathogenesis of NEC, are unknown.Here we analyze the role of FXR in IECs under NEC.
Project description:Necrotizing enterocolitis (NEC) is a prevalent pediatric emergency characterized by the sudden onset of intestinal ischemia and necrosis resulting from hyperinflammation.The interactions between the bile acid receptor FXR with gut microbiota and mucosal immunity in early postnatal life, and its exact role in the pathogenesis of NEC, are unknown.Here we analyze the role of FXR in IECs under NEC.
Project description:Necrotizing enterocolitis (NEC) is a devastating intestinal inflammatory disorder that primarily affects premature infants. Despite decades of research, this disease remains a significant cause of death in the absence of efficient therapeutics. Interleukin (IL)-22 has been shown to play a critical role in maintaining the gut barrier, promoting epithelial regeneration, and controlling intestinal inflammation in adult animal models with an established microbiome. However, the importance of IL-22 signaling in the regulation of gut homeostasis and protection in neonates that lack an established microbiome remains unknown. Therefore, the aim of the current study is to investigate the role of IL-22 in the neonatal intestinal epithelium under homeostatic and inflammatory conditions by using a mouse model of NEC. Our data reveal that Il22 expression in neonatal murine intestine is negligible until weaning. In addition, both human and murine neonates lack IL-22 production during NEC. Mice deficient in IL-22 or mice lacking the expression of IL-22 receptor in intestinal epithelial cells, display a similar susceptibility of neonates to NEC consistent with the lack of endogenous IL-22 at this critical stage of intestinal development. Conversely, treatment with recombinant IL-22 during NEC substantially reduces disease severity. This IL-22-mediated protection is associated with enhanced epithelial regeneration and increased expression of several antimicrobial genes. Strikingly, despite an IL-22-mediated induction of an antimicrobial transcriptional program, the composition of the intestinal microbial communities remains unchanged. Taken together, this study demonstrates that an IL-22 signaling axis promotes protection against neonatal NEC through the induction of epithelial cell regeneration.
