Jingren Zhong , Sebastian Høj Johansen , Ole Bæk , Duc Ninh Nguyen
{"title":"Citrulline supplementation exacerbates sepsis severity in infected preterm piglets via early induced immunosuppression","authors":"Jingren Zhong , Sebastian Høj Johansen , Ole Bæk , Duc Ninh Nguyen","doi":"10.1016/j.jnutbio.2024.109674","DOIUrl":null,"url":null,"abstract":"<div><p>Arginine (ARG)/Citrulline (CIT) deficiency is associated with increased sepsis severity after infection. Supplementation of CIT to susceptible patients with ARG/CIT deficiency such as preterm newborns with suspected infection might prevent sepsis, via maintaining immune and vascular function. Caesarean-delivered, parenterally nourished preterm pigs were treated with CIT (1g/kg bodyweight) via oral or continuous intravenous supplementation, then inoculated with live <em>Staphylococcus epidermidis</em> and clinically monitored for 14 h. Blood, liver, and spleen samples were collected for analysis. <em>In vitro</em> cord blood stimulation was performed to explore how CIT and ARG affect premature blood cell responses. After infection, oral CIT supplementation led to higher mortality, increased blood bacterial load, and systemic and hepatic inflammation. Intravenous CIT administration showed increased inflammation and bacterial burdens without significantly affecting mortality. Liver transcriptomics and data from <em>in vitro</em> blood stimulation indicated that CIT induces systemic immunosuppression in preterm newborns, which may impair resistance response to bacteria at the early stage of infection, subsequently causing later uncontrollable inflammation and tissue damage. The early stage of CIT supplementation exacerbates sepsis severity in infected preterm pigs, likely via inducing systemic immunosuppression.</p></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"131 ","pages":"Article 109674"},"PeriodicalIF":4.8000,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0955286324001074/pdfft?md5=621ed60d5683bfa85e879fe7ff215c28&pid=1-s2.0-S0955286324001074-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Nutritional Biochemistry","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0955286324001074","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Arginine (ARG)/Citrulline (CIT) deficiency is associated with increased sepsis severity after infection. Supplementation of CIT to susceptible patients with ARG/CIT deficiency such as preterm newborns with suspected infection might prevent sepsis, via maintaining immune and vascular function. Caesarean-delivered, parenterally nourished preterm pigs were treated with CIT (1g/kg bodyweight) via oral or continuous intravenous supplementation, then inoculated with live Staphylococcus epidermidis and clinically monitored for 14 h. Blood, liver, and spleen samples were collected for analysis. In vitro cord blood stimulation was performed to explore how CIT and ARG affect premature blood cell responses. After infection, oral CIT supplementation led to higher mortality, increased blood bacterial load, and systemic and hepatic inflammation. Intravenous CIT administration showed increased inflammation and bacterial burdens without significantly affecting mortality. Liver transcriptomics and data from in vitro blood stimulation indicated that CIT induces systemic immunosuppression in preterm newborns, which may impair resistance response to bacteria at the early stage of infection, subsequently causing later uncontrollable inflammation and tissue damage. The early stage of CIT supplementation exacerbates sepsis severity in infected preterm pigs, likely via inducing systemic immunosuppression.
期刊介绍:
Devoted to advancements in nutritional sciences, The Journal of Nutritional Biochemistry presents experimental nutrition research as it relates to: biochemistry, molecular biology, toxicology, or physiology.
Rigorous reviews by an international editorial board of distinguished scientists ensure publication of the most current and key research being conducted in nutrition at the cellular, animal and human level. In addition to its monthly features of critical reviews and research articles, The Journal of Nutritional Biochemistry also periodically publishes emerging issues, experimental methods, and other types of articles.