Human
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ABSTRACT:
PROVIDER: PRJNA475630 | ENA |
REPOSITORIES: ENA
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Project description:Early life inter-domain interactions shape the immunological environment of the airways
| PRJNA694493 | ENA
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:Microbial exposure during development can elicit long-lasting effects on the health of an individual. However, how microbial exposure in early life leads to permanent changes in the immune system is unknown. Here, we show that the microbial environment alters the setpoint for immune susceptibility by altering the developmental architecture of the CD8+ T cell compartment. In particular, early microbial exposure results in the preferential expansion of highly responsive fetal-derived CD8+ T cells that persist into adulthood and provide the host with enhanced immune protection against intracellular pathogens. Interestingly, microbial education of fetal-derived CD8+ T cells occurs during thymic development rather than in the periphery and involves the acquisition of a more effector-like epigenetic program. Collectively, our results provide a new conceptual framework for understanding how microbial colonization in early life leads to lifelong, and potentially irreversible, changes in the immune system.
2022-12-04 | GSE213830 | GEO
Project description:Microbial exposure during development can elicit long-lasting effects on the health of an individual. However, how microbial exposure in early life leads to permanent changes in the immune system is unknown. Here, we show that the microbial environment alters the setpoint for immune susceptibility by altering the developmental architecture of the CD8+ T cell compartment. In particular, early microbial exposure results in the preferential expansion of highly responsive fetal-derived CD8+ T cells that persist into adulthood and provide the host with enhanced immune protection against intracellular pathogens. Interestingly, microbial education of fetal-derived CD8+ T cells occurs during thymic development rather than in the periphery and involves the acquisition of a more effector-like epigenetic program. Collectively, our results provide a new conceptual framework for understanding how microbial colonization in early life leads to lifelong, and potentially irreversible, changes in the immune system.
2022-12-04 | GSE213829 | GEO
Project description:The study investigated the impact of environment on the composition of the gut microbiota and mucosal immune development and function at gut surfaces in early and adult life. Piglets of similar genotype were reared in indoor and outdoor environments and in an experimental isolator facility. Mucosa-adherent microbial diversity in the pig ileum was characterized by sequence analysis of 16S rRNA gene libraries. Host-specific gene responses in gut ileal tissues to differences in microbial composition were investigated using Affymetrix microarray technology and Real-time PCR.
2009-12-01 | GSE15256 | GEO
Project description:Transcriptional analysis of immunological characteristics of petstore mice, C57Bl/6 laboratory mice, and C57Bl/6 laboratory mice cohoused with petstore. We hypothesized that cohousing would confer a basal transcriptional signature of immune activation to laboratory mice from petstore mice. Comparison of these data with existing human adult vs. neonatal PBMC expression profiling data (GSE27272) revealed close concordance of laboratory mice with human neonates, and of cohoused or petstore mice with human adults. Results highlight the impact of environment on the basal immune state and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modeling immunological events in free-living organisms, including humans.
2016-03-09 | GSE78979 | GEO
Project description:National screening programs use dried blood specimens to detect abnormal metabolism or aberrant protein function in infants shortly after birth, thus identifying disorders that are not clinically evident in the newborn period. Gut microbiota metabolites and immunological acute phase proteins are capable of revealing potential immune aberrations. Microbial metabolites interact with xenobiotic receptors (i.e., aryl hydrocarbon and pregnane-X) and maintain gastrointestinal tissue health, supported by acute-phase proteins, functioning as sensors of microbial immunomodulation and homeostasis. The delivery mode (vaginal or cesarean section) shapes the microbial colonization, which substantially modulates both the immune system's response and mucosal homeostasis.
This study profiled microbial metabolites of the kynurenine and tryptophan pathway and acute phase proteins in 134 neonatal dried blood specimens. We newly established neonatal blood levels of the aryl hydrocarbon receptor microbial ligands (indole-3-aldehyde, indole-3-butyric acid, and indole-3-acetamide) on the second day of life. Furthermore, we observed divergent microbial metabolic profiles in neonates born vaginally or via cesarean section, hypothesizing potential microbial immunomodulatory influence. In summary, these findings suggest the supportive role of human gut microbiota in developing and maintaining immune system homeostasis.
2022-08-02 | PXD027606 | panorama
Project description:Transcriptional analysis of immunological characteristics of petstore mice, C57Bl/6 laboratory mice, and C57Bl/6 laboratory mice cohoused with petstore. We hypothesized that cohousing would confer a basal transcriptional signature of immune activation to laboratory mice from petstore mice. Comparison of these data with existing human adult vs. neonatal PBMC expression profiling data (GSE27272) revealed close concordance of laboratory mice with human neonates, and of cohoused or petstore mice with human adults. Results highlight the impact of environment on the basal immune state and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modeling immunological events in free-living organisms, including humans. Total RNA was isolated from PBMC of C57Bl/6 laboratory mice, petstore mice and C57Bl/6 laboratory mice cohoused with petstore mice (at least after 60 days post-cohousing)and transcriptional comparison among 3 groups were performed.
2016-03-09 | E-GEOD-78979 | 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