Ontology highlight
ABSTRACT:
PROVIDER: PRJNA717136 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Inappropriate cross talk between mammals and their gut microbiota may trigger intestinal inflammation and drive extra-intestinal immune-mediated diseases. Studies with germ-free or gnotobiotic animals represent the gold standard for research on bacterial-host interaction but they are not readily accessible to the wide scientific community. We aimed at refining a protocol that in a robust manner would deplete murine intestinal microbiota and prove to have significant biologic validity. Previously published protocols for depleting mice of their intestinal microbiota by administering broad-spectrum antibiotics in drinking water were difficult to reproduce. We show that twice daily delivery of antibiotics by gavage depleted mice of their cultivable fecal microbiota and reduced the fecal bacterial DNA load by approximately 400 fold while ensuring the animals’ health. Mice subjected to the protocol for 17 days displayed enlarged ceca, reduced Peyer’s patches and small spleens. Antibiotic treatment significantly reduced the expression of antimicrobial factors and altered the expression of 517 genes in total in the colonic epithelium. Genes involved in cell cycle were significantly altered concomitant with reduced epithelial proliferative activity in situ assessed by Ki-67 expression, suggesting that commensal microbiota drives cellular proliferation in colonic epithelium. We present a robust protocol for depleting mice of their cultivatable intestinal microbiota with antibiotics by gavage and show that the biological effect of this depletion is phenotypic characteristics and epithelial gene expression profile similar to those of germ-free mice. Comparison of genome-wide gene expression of colon intestinal epithelial cells from mice subjected to microbiota depletion protocol against to control mice.
2011-08-14 | E-GEOD-22648 | biostudies-arrayexpress
Project description:Inappropriate cross talk between mammals and their gut microbiota may trigger intestinal inflammation and drive extra-intestinal immune-mediated diseases. Studies with germ-free or gnotobiotic animals represent the gold standard for research on bacterial-host interaction but they are not readily accessible to the wide scientific community. We aimed at refining a protocol that in a robust manner would deplete murine intestinal microbiota and prove to have significant biologic validity. Previously published protocols for depleting mice of their intestinal microbiota by administering broad-spectrum antibiotics in drinking water were difficult to reproduce. We show that twice daily delivery of antibiotics by gavage depleted mice of their cultivable fecal microbiota and reduced the fecal bacterial DNA load by approximately 400 fold while ensuring the animals’ health. Mice subjected to the protocol for 17 days displayed enlarged ceca, reduced Peyer’s patches and small spleens. Antibiotic treatment significantly reduced the expression of antimicrobial factors and altered the expression of 517 genes in total in the colonic epithelium. Genes involved in cell cycle were significantly altered concomitant with reduced epithelial proliferative activity in situ assessed by Ki-67 expression, suggesting that commensal microbiota drives cellular proliferation in colonic epithelium. We present a robust protocol for depleting mice of their cultivatable intestinal microbiota with antibiotics by gavage and show that the biological effect of this depletion is phenotypic characteristics and epithelial gene expression profile similar to those of germ-free mice.
2011-08-15 | GSE22648 | GEO
Project description:Broad-spectrum antibiotics are frequently prescribed to children. The period of early-childhood represents a time where the developing microbiota may be more sensitive to environmental perturbations, which thus might have long-lasting host consequences. We hypothesized that even a single early-life broad-spectrum antibiotic course at a therapeutic dose (PAT) leads to durable alterations in both the gut microbiota and host immunity. In C57BL/6 mice, a single early-life tylosin (macrolide) course markedly altered the intestinal microbiome, and affected specific intestinal T-cell populations and secretory IgA expression, but PAT-exposed adult dams had minimal immunologic alterations. No immunological effects were detected in PAT-exposed germ-free animals; indicating that microbiota are required for the observed activities. Together these results indicate the impact of a single therapeutic early-life antibiotic course altering the microbiota and modulating host immune phenotypes that persist long after exposure has ceased.
2017-09-19 | E-MTAB-5101 | biostudies-arrayexpress
Project description:The early life microbiome plays important roles in host immunological and metabolic development. Because type 1 diabetes (T1D) incidence has been increasing substantially in recent decades, we hypothesized that early-life antibiotic use alters gut microbiota that predisposes to disease. Using NOD mice that are genetically susceptible to T1D, we examined the effects of exposure to either continuous low-dose antibiotics or pulsed therapeutic antibiotics (PAT) early in life, mimicking childhood exposures. We found that in mice receiving PAT, T1D incidence was significantly higher, microbial community composition and structure differed compared with controls. In pre-diabetic male PAT mice, the intestinal lamina propria had lower Th17 and T reg proportions and intestinal SAA expression than in controls, suggesting key roles in transducing the altered microbiota signals. PAT affected microbial lipid metabolism and host cholesterol biosynthetic gene expression. These findings show that early-life antibiotic treatments alter the gut microbiota and its metabolic capacities, intestinal gene expression, and T-cell populations, accelerating T1D onset in NOD mice.
2016-05-20 | GSE81648 | GEO
Project description:Intestinal macrophages were isolated from the intestine of mice that had been administered antibiotics for 7 days, prior to 7 days or re-exposure to the microbiota (recolonisation). In some experiments, the short-chain fatty acid butyrate was administered alongside antibiotics prior to recolonisation.
2019-07-22 | E-MTAB-7132 | biostudies-arrayexpress
Project description:Acquisition of the intestinal microbiota begins at birth, and a stable microbial community develops from a succession of key organisms. Disruption of the microbiota during maturation by low-dose antibiotic exposure can alter host metabolism and adiposity. We now show that low-dose penicillin (LDP), delivered from birth, induces metabolic alterations and affects ileal expression of genes involved in immunity. LDP that is limited to early life transiently perturbs the microbiota, which is sufficient to induce sustained effects on body composition, indicating that microbiota interactions in infancy may be critical determinants of long-term host metabolic effects. In addition, LDP enhances the effect of high-fat diet induced obesity. The growth promotion phenotype is transferrable to germ-free hosts by LDP-selected microbiota, showing that the altered microbiota, not antibiotics per se, play a causal role. These studies characterize important variables in early-life microbe-host metabolic interaction and identify several taxa consistently linked with metabolic alterations. C57BL6J mice received low-dose penicillin through their drinking water (6.7 mg/L), control mice did not receive antibiotics. All mice were started on normal chow (13.5% fat kcal). At 17 weeks of age, half of the mice were switched to high fat diet (45% fat kcal). Livers were collected at age 30 weeks, RNA was extracted, and transcriptional differences were measured by microarray analysis.
2014-09-01 | E-GEOD-58086 | biostudies-arrayexpress
Project description:Instability in the composition of gut bacterial communities, referred as dysbiosis, has been associated with important human intestinal disorders such as CrohnM-bM-^@M-^Ys disease and colorectal cancer. Here, we show that dysbiosis coupled to Nod2 or Rip2 deficiency suffices to cause an increased risk for intestinal inflammation and colitis-associated carcinogenesis in mice. Aggravated epithelial lesions and dysplasia upon chemical-induced injury associated with loss of Nod2 or Rip2 can be prevented by antibiotics or anti-IL6R treatment. Nod2-mediated risk for intestinal inflammation and colitis-associated tumorigenesis is communicable through maternally-transmitted microbiota even to wild-type hosts. Disease progression was identified to drive complex NOD2-dependent changes of the colonic-associated microbiota. Reciprocal microbiota transplantation rescues the vulnerability of Nod2-deficient mice to colonic injury. Altogether, our results unveil an unexpected function for NOD2 in shaping a protective assembly of gut microbial communities, providing a rationale for intentional manipulation of genotype-dependent dysbiosis as a causative therapeutic principle in chronic intestinal inflammation. Analysis used RNA extracted from colonic mucosa of untreated, antibiotics-treated or metronidazole-treated C57Bl/6J and Nod2-deficient mice in CAC model. Direct comparisons were performed as follow: C57Bl/6J untreated mice vs Nod2-deficient untreated mice, C57Bl/6J antibiotics-treated mice vs Nod2-deficient antibiotics-treated mice, C57Bl/6J metronidazole-treated mice vs Nod2-deficient metronidazole-treated mice, C57Bl/6J untreated mice vs C57Bl/6J antibiotics-treated mice, C57Bl/6J untreated mice vs C57Bl/6J metronidazole-treated mice, Nod2-deficient untreated mice vs Nod2-deficient antibiotics-treated mice, Nod2-deficient untreated mice vs Nod2-deficient metronidazole-treated mice. Indirect comparisons with control data were made across multiple arrays with raw data pulled from different channels for data analysis.
2013-01-02 | E-GEOD-32421 | biostudies-arrayexpress
Project description:Broad-spectrum antibiotics are frequently prescribed to children. The period of early-childhood represents a time where the developing microbiota may be more sensitive to environmental perturbations, which thus might have long-lasting host consequences. We hypothesized that even a single early-life broad-spectrum antibiotic course at a therapeutic dose (PAT) leads to durable alterations in both the gut microbiota and host immunity. In C57BL/6 mice, a single early-life tylosin (macrolide) course markedly altered the intestinal microbiome, and affected specific intestinal T-cell populations and secretory IgA expression, but PAT-exposed adult dams had minimal immunologic alterations. No immunological effects were detected in PAT-exposed germ-free animals; indicating that microbiota are required for the observed activities. Transfer of PAT-perturbed microbiota led to delayed sIgA expression indicating that the altered microbiota is sufficient to transfer PAT-induced effects. PAT exposure had lasting and transferable effects on microbial community network structure. Together these results indicate the impact of a single therapeutic early-life antibiotic course altering the microbiota and modulating host immune phenotypes that persist long after exposure has ceased.
2017-09-18 | GSE98291 | GEO
Project description:Broad-spectrum antibiotics are frequently prescribed to children. The period of early-childhood represents a time where the developing microbiota may be more sensitive to environmental perturbations, which thus might have long-lasting host consequences. We hypothesized that even a single early-life broad-spectrum antibiotic course at a therapeutic dose (PAT) leads to durable alterations in both the gut microbiota and host immunity. In C57BL/6 mice, a single early-life tylosin (macrolide) course markedly altered the intestinal microbiome, and affected specific intestinal T-cell populations and secretory IgA expression, but PAT-exposed adult dams had minimal immunologic alterations. No immunological effects were detected in PAT-exposed germ-free animals; indicating that microbiota are required for the observed activities. Transfer of PAT-perturbed microbiota led to delayed sIgA expression indicating that the altered microbiota is sufficient to transfer PAT-induced effects. PAT exposure had lasting and transferable effects on microbial community network structure. Together these results indicate the impact of a single therapeutic early-life antibiotic course altering the microbiota and modulating host immune phenotypes that persist long after exposure has ceased.
2017-09-18 | GSE98022 | GEO
Project description:We analyzed the effects of antibiotics using a popular model of gut microbiota depletion in mice by a cocktail of antibiotics. We combined intestinal transcriptome together with metagenomic analysis of the gut microbiota to develop a new bioinformatics approach that probes the links between microbial components and host functions. We found that most antibiotic-induced alterations can be explained by three factors: depletion of the microbiota; direct effects of antibiotics on host tissues; and the effects of remaining antibiotic-resistant microbes. While microbe depletion led to down-regulation of immunity, the two other factors primarily inhibited mitochondrial gene expression and amounts of active mitochondria, and induced cell death. By reconstructing and analyzing a transkingdom network, we discovered that these toxic effects were mediated by virulence/quorum sensing in antibiotic-resistant bacteria. This series includes gene expression in the ileum of control, antibiotics (ABx)-treated, germfree, germfree-ABx-treated and mice colonized with normal or Abx-resistant microbiota. common reference design with a pool of small intestine RNA labeled with Cy3
2015-01-26 | E-GEOD-60566 | biostudies-arrayexpress