Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1033905 | ENA |
REPOSITORIES: ENA
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Project description:A human gut-on-a-chip microdevice was used to coculture multiple commensal microbes in contact with living human intestinal epithelial cells for more than a week in vitro and to analyze how gut microbiome, inflammatory cells, and peristalsis-associated mechanical deformations independently contribute to intestinal bacterial overgrowth and inflammation. This in vitro model replicated results from past animal and human studies, including demonstration that probiotic and antibiotic therapies can suppress villus injury induced by pathogenic bacteria. By ceasing peristalsis-like motions while maintaining luminal flow, lack of epithelial deformation was shown to trigger bacterial overgrowth similar to that observed in patients with ileus and inflammatory bowel disease. Analysis of intestinal inflammation on-chip revealed that immune cells and lipopolysaccharide endotoxin together stimulate epithelial cells to produce four proinflammatory cytokines (IL-8, IL-6, IL-1β, and TNF-α) that are necessary and sufficient to induce villus injury and compromise intestinal barrier function. Thus, this human gut-on-a-chip can be used to analyze contributions of microbiome to intestinal pathophysiology and dissect disease mechanisms in a controlled manner that is not possible using existing in vitro systems or animal models. 6 samples, 2 biological replicates for each 3 conditions.
2015-12-16 | E-GEOD-65790 | biostudies-arrayexpress
Project description:enzymes. However, many genes in the microbiome remain uncharacterized due to the challenge in culturing intestinal strains in vitro, which limits the identification of target enzymes. To address this issue, we developed an effective Activity-Based MetaProteomics (ABMP) strategy using a specific activity-based probe (ABP) to screen the entire gut microbiome for target enzymes, without the need to isolate and culture bacterial strains individually. α-Galactosidases (AGALs) are widely distributed in gut microbiota, plant, and animal kingdoms of life and have multiple applications in industries such as food, animal feed, and biomedical sectors. Despite the rich source of AGALs in the gut microbiome, many AGAL genes lack functional annotations. Using an activity-based cyclophellitol aziridine probe specific to AGAL, we successfully identified and characterized several new enzymes possessing AGAL activities from the gut microbiome.
2023-08-25 | PXD044848 |
Project description:The gut microbiome is a malleable microbial community that can remodel in response to various factors, including diet, and contribute to the development of several chronic diseases, including atherosclerosis. We devised an in vitro screening protocol of the mouse gut microbiome to discover molecules that can selectively modify bacterial growth. This approach was used to identify cyclic D,L-α-peptides that remodeled the Western diet (WD) gut microbiome toward the low-fat-diet microbiome state. Daily oral administration of the peptides in WD-fed LDLr-/- mice reduced plasma total cholesterol levels and atherosclerotic plaques. Depletion of the microbiome with antibiotics abrogated these effects. Peptide treatment reprogrammed the microbiome transcriptome, suppressed the production of pro-inflammatory cytokines (including interleukin-6, tumor necrosis factor-α and interleukin-1β), rebalanced levels of short-chain fatty acids and bile acids, improved gut barrier integrity and increased intestinal T regulatory cells. Directed chemical manipulation provides an additional tool for deciphering the chemical biology of the gut microbiome and might advance microbiome-targeted therapeutics.
2019-12-31 | GSE104913 | GEO
Project description:The gut microbiome is a malleable microbial community that can remodel in response to various factors, including diet, and contribute to the development of several chronic diseases, including atherosclerosis. We devised an in vitro screening protocol of the mouse gut microbiome to discover molecules that can selectively modify bacterial growth. This approach was used to identify cyclic D,L-α-peptides that remodeled the Western diet (WD) gut microbiome toward the low-fat-diet microbiome state. Daily oral administration of the peptides in WD-fed LDLr-/- mice reduced plasma total cholesterol levels and atherosclerotic plaques. Depletion of the microbiome with antibiotics abrogated these effects. Peptide treatment reprogrammed the microbiome transcriptome, suppressed the production of pro-inflammatory cytokines (including interleukin-6, tumor necrosis factor-α and interleukin-1β), rebalanced levels of short-chain fatty acids and bile acids, improved gut barrier integrity and increased intestinal T regulatory cells. Directed chemical manipulation provides an additional tool for deciphering the chemical biology of the gut microbiome and might advance microbiome-targeted therapeutics.
2019-12-31 | GSE104914 | GEO
Project description:A human gut-on-a-chip microdevice was used to coculture multiple commensal microbes in contact with living human intestinal epithelial cells for more than a week in vitro and to analyze how gut microbiome, inflammatory cells, and peristalsis-associated mechanical deformations independently contribute to intestinal bacterial overgrowth and inflammation. This in vitro model replicated results from past animal and human studies, including demonstration that probiotic and antibiotic therapies can suppress villus injury induced by pathogenic bacteria. By ceasing peristalsis-like motions while maintaining luminal flow, lack of epithelial deformation was shown to trigger bacterial overgrowth similar to that observed in patients with ileus and inflammatory bowel disease. Analysis of intestinal inflammation on-chip revealed that immune cells and lipopolysaccharide endotoxin together stimulate epithelial cells to produce four proinflammatory cytokines (IL-8, IL-6, IL-1β, and TNF-α) that are necessary and sufficient to induce villus injury and compromise intestinal barrier function. Thus, this human gut-on-a-chip can be used to analyze contributions of microbiome to intestinal pathophysiology and dissect disease mechanisms in a controlled manner that is not possible using existing in vitro systems or animal models.
2015-12-16 | GSE65790 | GEO
Project description:The gut microbiome is a complex ecosystem stratified that varies along different sections of the gut. It comprises a wide array of metabolites originating from both food, host, and microbes. Microbially-derived metabolites, such as bile acids, short-chain fatty acids, and indole derivatives, are of significant interest due to their direct interactions with host physiology and regulating function. Most current studies on the gut microbiome focus on fecal samples, which do not fully represent the upper parts of the gut due to its stratification. To collect microbiome samples from the proximal gut microbiome, endoscopic methods or new non-invasive medical devices can be used. To enable comprehensive profiling of the gut metabolome and analyze key metabolites, we developed a combined approach combining untargeted and semi-targeted metabolomics using a Q-Exactive Plus Orbitrap mass spectrometer. Initially, we selected 49 metabolites of interest for the gut metabolome based on four distinct criteria. We validated these metabolites through repeatability and linearity tests and created a compound database using the software TraceFinder (ThermoFisher Scientific). For untargeted metabolomics, we established a workflow for the annotation and discovery of molecules. Finally, 37 metabolites were validated for semi-targeted metabolomics, and we conducted a proof of concept on small intestinal and fecal samples form a clinical trial (NCT05477069). Our combined approach, facilitated by molecular networking, demonstrated the potential to discover new metabolites.
| MSV000095801 | MassIVE
Project description:The intestinal microbiome forms dynamic ecosystem whose balanced composition and functioning are essential for maintaining overall gut health and well-being in living organisms. In broilers, dysbiosis disrupts the microbiota-host balance, often without obvious clinical symptoms but with intestinal inflammation, leading to impaired animal performance and significant economic losses. This study utilizes an in vivo model of dysbiosis to investigate the blood proteome response of broilers to intestinal imbalance. Microscopic histological changes in the gut (shorter villi, increased crypt depth, p<0.0001) were observed in the duodenal and jejunal tissue of challenged birds. Elevated levels of permeability markers faecal ovotransferrin (p < 0.0001) and serum iohexol (p= 0.0009) additionally indicated increased intestinal permeability in challenged group compared to control. The MS/MS-based proteomics analysis was performed on broilers’ blood plasma enabling identification of 388 proteins, 25 of which demonstrated significant difference between the groups. Functional analysis showed activation of immune response, signalling, and interspecies interaction, while proteins related to cellular physiology, cell-cell communication, and extracellular matrix (ECM) processes were suppressed. Protein-protein interaction (PPI) analysis revealed two clusters of downregulated proteins involved in ECM organization and cell adhesion. These results suggest that the dysbiosis challenge alters plasma protein expression as the host prioritizes immune defense over structural maintenance. The activation of immune processes and suppression of ECM pathways highlight potential biomarkers and therapeutic targets for addressing dysbiosis.
2025-07-14 | PXD056546 | Pride
Project description:The neurotoxic effects and mechanisms of low-dose and long-term sulfamethoxazole (SMZ) exposure remain unknown. This study exposed zebrafish to environmental SMZ concentrations and observed behavioral outcomes. SMZ exposure increased hyperactivity and altered the transcript levels of 17 genes associated with neurological function. It impaired intestinal function by reducing the number of intestinal goblet cells and lipid content. Metabolomic results indicated that the contents of several lipids and amino acids in the gut were altered, which might affect the expression levels of neurological function-related genes. Metagenomic results demonstrated that SMZ exposure substantially altered the composition of the gut microbiome. Zebrafish receiving a transplanted fecal microbiome from the SMZ group were also found to exhibit abnormal behavior, suggesting that the gut microbiome is an important target for SMZ exposure-induced neurobehavioral abnormalities. Multi-omics correlation analysis revealed that gut micrometabolic function was related to differential gut metabolite levels, which may affect neurological function through the gut-brain-axis. Reduced abundance of Lefsonia and Microbacterium was strongly correlated with intestinal metabolic function and may be the key bacterial genera in neurobehavioral changes. This study confirms for the first time that SMZ-induced neurotoxicity in zebrafish is closely mediated by alterations in the gut microbiome.
2024-02-22 | GSE255986 | GEO