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:Background: Prevention of hyperlipidemia and associated diseases is a health priority. Complementary medicine based on scientific evidence has recently recognized the potential of natural products for modulating lipid metabolism, such as the medicinal mushroom Ganoderma lucidum (Gl), which possesses hypocholesterolemic, prebiotic and antidiabetic properties. Methods: Whole-transcriptomic changes in liver and kidney from a mouse model (C57BL/6), under a high-cholesterol diet and standardized Gl extracts (Gl-1, Gl-2) or simvastatin administration, were analyzed to determine Gl hypocholesterolemic activity. Further effects of Gl extracts on lipid metabolism were evaluated using an in vitro hepatic-like macrophage model. Additionally, correlations among hepatic gene expression, microbiota and serum lipid profiles in vivo established by Gl extracts were evaluated. Results: Based on the hepatic and renal mRNA profiles of mice treated with Gl extracts and high-cholesterol diet, we identified relevant metabolic pathways modulated by Gl involving the restriction of lipid biosynthesis and the enrichment of lipid degradation and secretion. We further showed that Gl extracts induce a significant decrease of macrophage lipid storage and cholesterol biosynthesis, which occurs concomitantly by the down-modulation of Fasn and Elovl6. We also determined that prebiotic effects of Gl extracts modulating gut microbiota are correlated with the gene expression portraits. Conclusions: Our high-throughput analysis allowed to identify key transcriptomic nodes established by Gl extracts and their interaction with microbiome composition related to lipid catabolic signaling. Our results indicated that our Gl extracts have a robust potential to be used as transcriptome modulators and prebiotic agents to prevent metabolic disorders associated to hypercholesterolemia.
Project description:We systematically assessed the transcriptomic changes of circulating leukocytes from whole blood of mice that had undergone polymicrobial sepsis. We systematically assessed the transcriptomic changes of liver tissue of mice that had undergone polymicrobial sepsis. Data indicate strong dissimilarities in early gene expression during murine sepsis affecting several pathways such as Toll-like receptor signalling, MAPK signalling, cytokine-cytokine receptor interaction, chemokine-signalling, and apoptosis during murine sepsis.
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:This study use different ice recrystalization inhibitors (IRIs) for better storing live microbiota. We evaluated whether the addition of IRIs can improve the cultivibility of microbiome and maintain their resposnes to prebiotic kestose. Frozen or fresh microbiota were cultured with or without kestose for 24 hours, and microbiota samples were collected for metaproteomics analysis.
Project description:This work investigates the effects of a prebiotic mix containing lutein, zeaxanthin, and saffron, recognized for their anti-inflammatory properties, on ophthalmological and microbial parameters in neovascular AMD (nAMD) patients.
Project description:BACKGROUND:Fecal microbiota transfer (FMT) is increasingly being used in Ger- many, as in other countries, for the treatment of recurrent Clostridioides difficile infection (rCDI). FMT is now being performed both for research and in individual patients outside of clinical trials. No compulsory standards have been established to date for donor screening or for the method of fecal transfer. Given the potential dangers of FMT, this would seem to be urgently necessary. METHODS:This review is based on pertinent literature retrieved by a selective search, including the reports of consensus conferences from Germany and abroad. RESULTS:Because of its high efficacy, FMT is the treatment of choice for rCDI. It is largely free of adverse side effects, even in immune-deficient patients, as long as comprehensive and repeated donor screening has been carried out, with extensive clinical and microbiological testing and with the use of structured questionnaires. The ingestion of frozen, encapsulated microbiota is just as effective as other modes of delivery for the treatment of rCDI. CONCLUSION:Encapsulation of the fecal microbiome (FM) and storage at -20°C is the method of choice, because it can be standardized with the necessary quality controls and it is readily available. Patients with rCDI should undergo FMT by orally ingesting the capsules. There are ongoing research efforts to identify the active e FM. It is not yet clear when the ultimate goal of recombinant production can be achieved.
Project description:This study aimed to investigate the effects of two Thai traditional recipes including Dapphitkhai and Chanthaleela on various immune parameters and signaling pathways in human white blood cells. The gene expression of whole blood stimulation was analyzed through RNA-sequencing and pathway analysis. Chanthaleela and Dapphitkhai demonstrated a significant decrease in IL-8 secretion and an increase in IFN-β secretion, suggesting their potential to modulate these signaling pathways. Gene expression analysis of Chanthaleela and Dapphitkhai at 500 µg/mL revealed distinct patterns and identified differentially expressed genes. Gene ontology analysis highlighted the impact of the recipes on immune responses and cytokine regulation, while pathway analysis identified key pathways related to cytokine-cytokine receptor interaction, chemokine signaling, and infection-related processes. This study provides valuable insights into the effects of Thai traditional recipes on immune parameters and signaling pathways in human white blood cells. The findings suggest potential therapeutic applications of Thai traditional medicine in immune-related disorders and viral infections like COVID-19.