Liver transcriptome of an LPS infusion model for porcine sepsis
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ABSTRACT:
ORGANISM(S): Sus scrofa
PROVIDER: GSE250039 | GEO | 2023/12/31
REPOSITORIES: GEO
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Project description:Liver transcriptome of an LPS infusion model for porcine sepsis
| PRJNA1051645 | ENA
Project description:Alterations in intestinal microbiota and intestinal short chain fatty acids profiles have been associated with the pathophysiology of obesity and insulin resistance. Whether intestinal microbiota dysbiosis is a causative factor in humans remains to be clarified We examined the effect of fecal microbial infusion from lean donors on the intestinal microbiota composition, glucose metabolism and small intestinal gene expression. Male subjects with metabolic syndrome underwent bowel lavage and were randomised to allogenic (from male lean donors with BMI<23 kg/m2, n=9) or autologous (reinfusion of own feces, n=9) fecal microbial transplant. Insulin sensitivity and fecal short chain fatty acid harvest were measured at baseline and 6 weeks after infusion. Intestinal microbiota composition was determined in fecal samples and jejunal mucosal biopsies were also analyzed for the host transcriptional response. Insulin sensitivity significantly improved six weeks after allogenic fecal microbial infusion (median Rd: from 26.2 to 45.3 μmol/kg.min, p<0.05). Allogenic fecal microbial infusion increased the overall amount of intestinal butyrate producing microbiota and enhanced fecal harvest of butyrate. Moreover, the transcriptome analysis of jejunal mucosal samples revealed an increased expression of genes involved in a G-protein receptor signalling cascade and subsequently in glucose homeostasis. Lean donor microbial infusion improves insulin sensitivity and levels of butyrate-producing and other intestinal microbiota in subjects with the metabolic syndrome. We propose a model wherein these bacteria provide an attractive therapeutic target for insulin resistance in humans. (Netherlands Trial Register NTR1776).
2020-10-28 | GSE30854 | GEO
Project description:The aim of this study was to test the hypothesis that replenishing the microbiota with a fecal microbiota transplant (FMT) can rescue a host from an advanced stage of sepsis. We developed a clinically-relevant mouse model of lethal polymicrobial gut-derived sepsis in mice using a 4-member pathogen community (Candida albicans, Klebsiella oxytoca, Serratia marcescens, Enterococcus faecalis) isolated from a critically ill patient. In order to mimic pre-operative surgical patient condition mice were exposed to food restriction and antibiotics. Approximately 18 hours prior to surgery food was removed from the cages and the mice were allowed only tap water. Each mouse received an intramuscular Cefoxitin injection 30 minutes prior to the incision at a concentration of 25 mg/kg into the left thigh. Mice were then subjected to a midline laparotomy, 30% hepatectomy of the left lateral lobe of the liver and a direct cecal inoculation of 200 µL of the four pathogen community. On postoperative day one, the mice were administered rectal enema. Mice were given either 1 ml of fecal microbiota transplant (FMT) or an autoclaved control (AC). This was again repeated on postoperative day two. Mice were then followed for mortality. Chow was restored to the cages on postoperative day two, approximately 45 hours after the operation. The injection of fecal microbiota transplant by enema significantly protected mice survival, reversed the composition of gut microflora and down-regulated the host inflammatory response. The cecum, left lobe of the liver, and spleen were isolated from mice for microarray processing with three or more replicates for six expermental conditions: non-treated control, SAHC POD1, SAHC.AC POD2, SAHC.FMT POD2, SAHC.AC POD7, SAHC.FMT POD7
2015-07-30 | E-GEOD-71530 | biostudies-arrayexpress
Project description:The CS and CLP murine models of intra-abdominal sepsis have unique transcriptomic respones 2 hrs, 1 and 3 days after sepsis We used mouse microarrays to detail the molecular profile of the events that occur following infection in two different sepsis models Infection protocol: Used the Cecal Ligation and Puncture (CLP) model and Cecal Slurry (CS) method in young mice.
2014-02-21 | E-GEOD-55238 | biostudies-arrayexpress
Project description:This study aimed to compare gene expression profiles between patients with sepsis and healthy volunteers, to determine the accuracy of these profiles in diagnosing sepsis, and to predict sepsis outcomes by combining bioinformatics data with molecular experiments and clinical information.
2023-05-19 | GSE232753 | GEO
Project description:Despite decades of research, sepsis remains one of the most urgent unmet medical needs. Clinical trials in sepsis have mainly focused on targeting the inflammatory pathway, however, recent data indicate that sepsis should also be seen as a metabolic disease. Targeting metabolic dysregulations that take place in sepsis might uncover novel therapeutic opportunities to treat human sepsis patients. The role of PPARα in liver dysfunction during sepsis has recently been described, and restoring PPARα signaling proves to be successful in murine sepsis. To find out whether this therapy might also be helpful in human sepsis patients, we analyzed metabolic perturbations in liver of a porcine fecal peritonitis model. Resuscitation with fluids, antimicrobial therapy and abdominal drainage were applied to the pigs in order to mimic human clinical care. By using RNA-seq, we detected problems with PPARα signaling in the livers of septic pigs and reduced PPARα levels correlated well with disease severity. As PPARα regulates the expression of many genes involved in FA oxidation, reduced expression of these target genes concomitant with increased FFAs in plasma and ectopic lipid deposition in the liver was observed. The results obtained in pigs are in agreement with earlier observations in mice and support the potential of targeting defective PPARα signaling in the clinic.
2022-11-28 | GSE218636 | GEO
Project description:Expression data from Total RNA extracted from murine spleen. Sepsis was induced in C57Bl/6J mice by cecal ligation and puncture (CLP), followed 6 hours later by an intravenous injection of Mesenchymal Stem Cell (MSC) or saline. Twenty-eight hours after CLP, plasma, bronchoalveolar lavage (BAL) fluid and tissues were collected for analyses. Total RNA was extracted using Trizol (as per manufactures' instruction) followed by clean-up procedure using Qiagen RNA easy Prep (as per manufactures instructions) In the following study we hypothesized that mesenchymal stem cells (MSCs), which have documented immunomodulatory properties, would reduce sepsis-associated inflammation and organ injury in a clinically relevant model of sepsis. To identify the molecular changes associated with decreased inflammation in CLP-injured mice treated with MSCs, we analyzed the gene expression profiles from spleens collected at 28 hours from 4 animals per group: sham/saline, CLP/saline, and CLP/MSCs.
2010-11-22 | E-GEOD-24357 | biostudies-arrayexpress
Project description:The aim of this study was to test the hypothesis that replenishing the microbiota with a fecal microbiota transplant (FMT) can rescue a host from an advanced stage of sepsis. We developed a clinically-relevant mouse model of lethal polymicrobial gut-derived sepsis in mice using a 4-member pathogen community (Candida albicans, Klebsiella oxytoca, Serratia marcescens, Enterococcus faecalis) isolated from a critically ill patient. In order to mimic pre-operative surgical patient condition mice were exposed to food restriction and antibiotics. Approximately 18 hours prior to surgery food was removed from the cages and the mice were allowed only tap water. Each mouse received an intramuscular Cefoxitin injection 30 minutes prior to the incision at a concentration of 25 mg/kg into the left thigh. Mice were then subjected to a midline laparotomy, 30% hepatectomy of the left lateral lobe of the liver and a direct cecal inoculation of 200 µL of the four pathogen community. On postoperative day one, the mice were administered rectal enema. Mice were given either 1 ml of fecal microbiota transplant (FMT) or an autoclaved control (AC). This was again repeated on postoperative day two. Mice were then followed for mortality. Chow was restored to the cages on postoperative day two, approximately 45 hours after the operation. The injection of fecal microbiota transplant by enema significantly protected mice survival, reversed the composition of gut microflora and down-regulated the host inflammatory response.
2015-07-30 | GSE71530 | GEO
Project description:Expression data from Total RNA extracted from murine spleen, liver, lungs, kidneys and hearts. Sepsis was induced in C57Bl/6J mice by cecal ligation and puncture (CLP), followed 6 hours later by an intravenous injection of Mesenchymal Stem Cell (MSC) or saline. Twenty-eight hours after CLP, plasma, bronchoalveolar lavage (BAL) fluid and tissues were collected for analyses. Total RNA was extracted using Trizol (as per manufactures' instruction) followed by clean-up procedure using Qiagen RNA easy Prep (as per manufactures instructions) In the following study we hypothesized that mesenchymal stem cells (MSCs), which have documented immunomodulatory properties, would reduce sepsis-associated inflammation and organ injury in a clinically relevant model of sepsis. To identify the molecular changes associated with decreased inflammation in CLP-injured mice treated with MSCs, we analyzed the gene expression profiles from spleens, liver, lungs, kidneys and heart collected at 28 hours from 4 animals per group: sham/saline, CLP/saline, and CLP/MSCs.
2012-12-31 | E-GEOD-40180 | biostudies-arrayexpress
Project description:Expression data from Total RNA extracted from murine spleen. Sepsis was induced in C57Bl/6J mice by cecal ligation and puncture (CLP), followed 6 hours later by an intravenous injection of Mesenchymal Stem Cell (MSC) or saline. Twenty-eight hours after CLP, plasma, bronchoalveolar lavage (BAL) fluid and tissues were collected for analyses. Total RNA was extracted using Trizol (as per manufactures' instruction) followed by clean-up procedure using Qiagen RNA easy Prep (as per manufactures instructions) In the following study we hypothesized that mesenchymal stem cells (MSCs), which have documented immunomodulatory properties, would reduce sepsis-associated inflammation and organ injury in a clinically relevant model of sepsis.
2010-11-22 | GSE24357 | GEO