Project description:<p>The intestinal microflora and metabolites produced by these microbes serve as important regulators of the development of sepsis. Accordingly, this study was designed to systematically explore the relationships between the regulation of septicemia and both the intestinal flora and fecal metabolites by examining the functional roles of metabolites in the protection against sepsis-associated intestinal damage. To that end, fecal and peripheral blood mononuclear cell (PBMC) samples were collected from sepsis patients and healthy controls. A series of longitudinal multi-omics analyses were then used to assess the links between the intestinal flora or associated metabolites and PBMCs in sepsis patients, while animal model studies were further used to probe the protective effects of intestinal flora-derived metabolites on intestinal damage and immunity in the context of sepsis. These analyses revealed that intestinal dysbiosis was a common finding in sepsis patients, which commonly exhibited higher levels of deleterious bacteria and/or reductions in beneficial bacteria. A machine learning approach was used to identify samples from sepsis patients, revealing that at the genus level, sepsis samples could be distinguished by the presence of Bifidobacterium, Bacteroides, Porphyromonas, Prevotell, Enterococcus, Anaerococcus and Veillonella species. Metabolomics analyses indicated that there were significant differences in the levels of intestinal flora-derived metabolites including L-serine, L-valine and L-tyrosine when comparing samples from the sepsis and control groups, while corresponding transcriptomic analyses of PBMC samples using an ImmunecellAI analytical approach revealed a significant sepsis-related increase in the abundance of T cells and Th17 cells. Single-cell sequencing data from sepsis-associated PBMCs was also downloaded from the GEO database, confirming the observation that Th17 cell levels and those of other immune cells rose significantly in the context of septicemia. Animal model experiments revealed that intestinal microbiota-derived L-valine was able to alleviate inflammation and protest against sepsis-induced intestinal damage by inhibiting Th17 cell activation. Overall, these results thus highlight the successful application of machine learning to distinguish between sepsis and control samples based on the composition of the intestinal flora while demonstrating the potential therapeutic benefits of L-valine as an inhibitor of Th17 cell activity that may offer value as a means of alleviating or preventing intestinal damage in treated individuals. </p>
Project description:Interventions: Colorectal cancer control group:no;Colorectal cancer probiotics group:No
Primary outcome(s): Intestinal flora metabolomics;Intestinal mucosal barrier;Inflammatory factors;Observation of clinical efficacy indicators;Intestinal flora
Study Design: Parallel
| 2759602 | ecrin-mdr-crc
Project description:GMRC cocktail regulate the intestinal flora of patients with sepsis invitro.
Project description:During extreme physiological stress, the intestinal tract can be transformed into a harsh environment characterized by regio- spatial alterations in oxygen, pH, and phosphate concentration. When the human intestine is exposed to extreme medical interventions, the normal flora becomes replaced by pathogenic species whose virulence can be triggered by various physico-chemical cues leading to lethal sepsis. We previously demonstrated that phosphate depletion develops in the mouse intestine following surgical injury and triggers intestinal P. aeruginosa to express a lethal phenotype that can be prevented by oral phosphate ([Pi]) supplementation.
Project description:To explore the regulatory mechanism of intestinal flora in Citrobacter rodentium -induced intestinal infection by transcriptome analysis at miRNA molecular level.
Project description:Drosophila melanogaster was used to investigate the influence of microbiota-derived intestinal flora and its metabolites on host transcriptional regulation by adding sodium butyrate to a sterile diet for constructing a sterile Drosophila model. In order to further investigate the effects of sodium butyrate on Drosophila melanogaster at the molecular mechanism level, we detected the abundance and composition of midgut microbial colonies based on 16S rRNA gene sequences, and analyzed the overall structure and metabolic activities of host transcriptional networks by combining transcriptome and non-target metabolomics data.
Project description:During extreme physiological stress, the intestinal tract can be transformed into a harsh environment characterized by regio- spatial alterations in oxygen, pH, and phosphate concentration. When the human intestine is exposed to extreme medical interventions, the normal flora becomes replaced by pathogenic species whose virulence can be triggered by various physico-chemical cues leading to lethal sepsis. We previously demonstrated that phosphate depletion develops in the mouse intestine following surgical injury and triggers intestinal P. aeruginosa to express a lethal phenotype that can be prevented by oral phosphate ([Pi]) supplementation. We used a microarray to define the virulence-related genes in P. aeruginosa grown as lawns on NGM at pH7.5 vs pH6.0 All samples for gene expression analysis were prepared in triplicate. P. aeruginosa MPAO1 cells collected from lawns grown on NGM/[Pi]25 mM, pH 6.0 or NGM/[Pi]25, pH 7.5 were used for RNA isolation as previously described. Microarray analysis was performed using Affymetrix P. aeruginosa GeneChips (Affymetrix, Santa Clara, CA) at the University of Chicago Functional Genomics Facility
Project description:Ulcerative colitis (UC), belonging to inflammatory bowel disease (IBD), is a chronic and relapsing inflammatory disorders of the gastrointestinal tract, which is not completely cured so far. Valeriana jatamansi is a Chinese medicine used clinically to treat "diarrhea", which is closely related to UC. This study was to elucidate the therapeutic effects of V. jatamansi extract (VJE) on dextran sodium sulfate (DSS)-induced UC in mice and its underlying mechanism. In this work, VJE effectively ameliorate the symptoms, histopathological scores and reduce the production of inflammatory factors of UC mice. The colon untargeted metabolomics analysis and 16S rDNA sequencing showed remarkable differences in colon metabolite profiles and intestinal microbiome composition between the control and DSS groups, and VJE intervention can reduce these differences. Thirty-two biomarkers were found and modulated the primary pathways including pyrimidine metabolism, arginine biosynthesis and glutathione metabolism. Meanwhile, twelve significant taxa of gut microbiota were found. Moreover, there is a close relationship between endogenous metabolites and intestinal flora. These findings suggested that VJE ameliorates UC by inhibiting inflammatory factors, recovering intestinal maladjustment, and regulating the interaction between intestinal microbiota and host metabolites. Therefore, the intervention of V. jatamansi is a potential therapeutic treatment for UC.