Project description:We used microarrays to detail the global signature of gene expression underlying endoscopic recurrence of CD and identified distinct gene signature predicting postoperative recurrence.
Project description:As a hallmark of Crohn's disease (CD),creeping fat (CF) is intimately related to intestinal fibrosis and postoperative recurrence. It is defined as expansion of mesenteric adipose tissue envelops the diseased intestinal segment. Compared with the healthy controls, CF has enriched functions related to adipogenesis and immune response.
Project description:Crohn's Disease (CD) is a chronic inflammatory disease of the intestinal tract. We performed a whole-genome transcriptional analysis using colonic biopsies from CD patients before and after anti-TNF-α therapy. Involved colonic samples from Crohn's disease patients and healthy colonic samples from non-inflammatory controls were collected for RNA extraction and hybridization on Affymetrix microarrays. Inclusion criteria for CD patients were: age between 18 and 70, diagnosis of CD established at least 4 months before inclusion and exclusion of concomitant infection. Active disease was defined by endoscopic and clinical score: endoscopic active disease was defined as a CD endoscopic index of severity (CDEIS) of 5 or more and the presence of large ulcers (> 0.5 cm diameter) in at least one of the explored segments. Clinical activity was defined as a CD activity index (CDAI) above 150. Finally, a total of 39 biopsies were analyzed: 17 healthy controls, 10 active CD without anti-TNF therapy, 5 active CD with anti-TNF therapy (non-responders) and 7 inactive CD with anti-TNF therapy (responders).
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
Project description:The aim of this study was to investigate differential intestinal gene expression in patients with Crohn's disease (CD) and controls. 172 biopsies from CD and control subjects were studied. Endoscopic biopsies were taken at ileocolonoscopy from five specific anatomical locations including the terminal ileum for RNA extraction.
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.
Project description:The aim of this study was to investigate differential intestinal gene expression in patients with Crohn's disease (CD) and controls. 172 biopsies from CD and control subjects were studied. Endoscopic biopsies were taken at ileocolonoscopy from five specific anatomical locations including the terminal ileum for RNA extraction. Biopsies from one of four anatomic locations, from healthy controls and treated (with non-biologic standard of care) or untreated CD patients.
Project description:Microarrays were used to analyze the gene expression in endoscopic-derived intestinal mucosal biopsies from patients with inflammatory bowel disease (IBD) and controls Mucosal biopsies were obtained at endoscopy from the colon of 97 ulcerative colitis (UC), 8 Crohn's disease (CD) patients and 11 controls. The biopsies were taken at the most affected sites but at a distance of ulcerations. Disease activity was endoscopically assessed. Total RNA extracted from mucosal biopsies was used to analyze mRNA expression via Affymetrix Human Gene 1.0 ST arrays