A balanced microbiota of the gastrointestinal tract (GIT) is a prerequisite for a healthy host. The GIT microbiota in preterm infants is determined by the method of delivery and nutrition. Probiotics can improve the GIT microbiota balance and suitable animal models are required to verify their harmlessness. Preterm gnotobiotic piglets were colonized with Lactobacillus rhamnosus GG (LGG) to evaluate its safety and possible protective action against infection with an enteric pathogen, Salmonella Typhimurium (ST). Clinical signs (anorexia, somnolence, fever and diarrhea), bacterial interference and translocation, intestinal histopathology, transcriptions of claudin-1, occludin and interferon (IFN)-γ, intestinal and systemic protein levels of interleukin (IL)-8, IL-12/23 p40 and IFN-γ were compared among (i) germ-free, (ii) LGG-colonized, (iii) ST-infected and (iv) LGG-colonized and subsequently ST-infected piglets for 24 h. Both LGG and ST-colonized the GIT; LGG translocated in some cases into mesenteric lymph nodes and the spleen but did not cause bacteremia and clinical changes. ST caused clinical signs of gastroenteritis, translocated into mesenteric lymph nodes, the spleen, liver and blood, increased claudin-1 and IFN-γ transcriptions, but decreased occludin transcription and increased local and systemic levels of IL-8 and IL-12/23 p40. Previous colonization with LGG reduced ST colonization in the jejunum and translocation into the liver, spleen and blood. It partially ameliorated histopathological changes in the intestine, reduced IL-8 levels in the jejunum and plasma and IL-12/23 p40 in the jejunum. The preterm gnotobiotic piglet model of the vulnerable preterm immunocompromised infant is useful to verify the safety of probiotics and evaluate their protective effect.
- MeSH
- bakteriální translokace MeSH
- cytokiny analýza MeSH
- gnotobiologické modely MeSH
- Lacticaseibacillus rhamnosus * MeSH
- prasata MeSH
- předčasný porod mikrobiologie MeSH
- probiotika farmakologie MeSH
- proteiny těsného spoje genetika MeSH
- Salmonella typhimurium růst a vývoj MeSH
- střeva mikrobiologie patologie MeSH
- střevní mikroflóra MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVE: The diagnosis of sepsis is difficult in immunocompromised patients owing to their modified response to infection. Our experiment in minipigs was designed to compare responses to sepsis between experimental groups of septic minipigs with and without immunosuppression. METHODS: Minipigs with identical baseline parameters were randomized into 3 groups: Sepsis (n = 10); immunosuppression (n = 11), including cyclosporine, methylprednisolone, and mycophenolate mofetil treatment before surgery, and a sham group (n = 6). Sepsis was induced by cecal ligation and puncture (CLP). We recorded selected clinical and laboratory parameters up to 24 hours postoperatively. RESULTS: All CLP animals developed septic shock with a febrile response, tachycardia, and hypotension requiring noradrenaline administration. The hemodynamic responses to sepsis in septic groups with and without immunosuppression were similar. Noradrenaline infusion was started on average later in the immunosuppression than in the group without immunosuppression; however, the difference was not significant. The kinetics of the plasma levels of most selected cytokines and C-reactive protein were similar in both septic groups. At 10 hours after surgery, the immunosuppression group showed significantly lower interleukin (IL)-6 levels compared with the sepsis group. At 19, 22, and 25 hours after surgery immunosuppressed animals displayed significantly greater increases in IL-10 levels compared with the cohort without immunosuppression. CONCLUSIONS: CLP is a simple, reproducible model of sepsis in minipigs. All CLP animals developed sepsis within 24 hours on average. Significant differences in IL-6 and IL-10 plasma levels were recorded between septic animals with versus without immunosuppression.
- MeSH
- biologické markery krev MeSH
- časové faktory MeSH
- cékum mikrobiologie chirurgie MeSH
- cyklosporin farmakologie MeSH
- hemodynamika MeSH
- hostitel s imunodeficiencí * MeSH
- imunosupresiva farmakologie MeSH
- kardiotonika farmakologie MeSH
- kyselina mykofenolová analogy a deriváty MeSH
- ligace MeSH
- mediátory zánětu krev MeSH
- methylprednisolon farmakologie MeSH
- miniaturní prasata MeSH
- modely nemocí na zvířatech MeSH
- noradrenalin farmakologie MeSH
- prasata MeSH
- punkce MeSH
- sepse krev farmakoterapie imunologie mikrobiologie patofyziologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- chov zvířat MeSH
- gnotobiologické modely MeSH
- prasata MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- MeSH
- finanční podpora výzkumu jako téma MeSH
- ileum mikrobiologie ultrastruktura MeSH
- interleukiny imunologie MeSH
- lymfatické uzliny imunologie mikrobiologie ultrastruktura MeSH
- mutace MeSH
- nemoci prasat imunologie mikrobiologie prevence a kontrola MeSH
- Salmonella typhimurium genetika imunologie patogenita MeSH
- salmonelová infekce u zvířat imunologie prevence a kontrola MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- MeSH
- amnion mikrobiologie ultrastruktura MeSH
- finanční podpora výzkumu jako téma MeSH
- fluorescenční protilátková technika MeSH
- imunohistochemie MeSH
- infekce vyvolané Escherichia coli metabolismus MeSH
- interleukin-18 biosyntéza genetika MeSH
- prasata MeSH
- těhotenství MeSH
- transmisní elektronová mikroskopie MeSH
- virulence MeSH
- zvířata MeSH
- Check Tag
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
- MeSH
- amnion imunologie mikrobiologie MeSH
- cytokiny analýza MeSH
- Escherichia coli patogenita MeSH
- finanční podpora výzkumu jako téma MeSH
- fluorescenční protilátková technika metody MeSH
- imunohistochemie metody MeSH
- infekce vyvolané Escherichia coli imunologie MeSH
- těhotenství MeSH
- zánět diagnóza imunologie MeSH
- zvířata MeSH
- Check Tag
- těhotenství MeSH
- zvířata MeSH
- MeSH
- amnion patologie MeSH
- bakteriální infekce mikrobiologie MeSH
- cytokiny biosyntéza MeSH
- mediátory zánětu fyziologie MeSH
- Publikační typ
- přehledy MeSH
