Similar Datasets
Project description:Early-life antibiotic-driven dysbiosis in mice is associated with impaired metabolism and immunity in later life and reduced lifespan.
| PRJNA646387 | ENA
Project description:ObjectivesEarly socioeconomic status (SES) correlates with later-life cognition. However, the effect of socioeconomic context (SEC), which reflects influences from broader ecological contexts, has not been examined. The present study developed a measure of SEC using lifetime residential addresses and examined SEC and residential mobility effects on later-life cognition.MethodOlder adults (N = 117, Mage = 75) reported addresses since birth. Latent SEC was constructed from census income, employment, and education (1920-2010) for each county and census year, extrapolated between census years. Controlling for current SES, SEC in childhood (ages 0-18) and adulthood (ages 19-60), with finer granulations in young adulthood (ages 19-39) and midlife (ages 40-60), predicted later-life cognition. Effects of residential mobility on later-life cognition were also examined.ResultsHigher childhood and adulthood SEC were associated with better Auditory Verbal Learning Test recognition (β = .24, p = .012) and immediate recall (β = .26, p = .008). Higher midlife SEC was associated with faster task switching (β = .26, p = .025) and better task switching efficiency (β = .27, p = .022). Higher residential mobility in childhood was associated with higher crystallized intelligence (β = .194, p = .040).DiscussionIndependent of current SES, childhood and adulthood SEC predicted later-life cognition, which may be sensitive to effects of social institutions and environmental health. SEC assessed across the lifespan, and related residential mobility information may be important complements to SES in predicting later-life cognitive health.
| S-EPMC6294237 | biostudies-literature
Project description:There is a marked dysregulation of the proteome as organisms age. Regulation of both protein production and degradation can become dysregulated as an organism ages. However, whether and how aging-responsive transcripts are selectively translated is unknown. Changes in the composition of the ribosome can lead to differential binding and translation of specific transcripts. Here we examined the role of ribosomal RNA (rRNA) methylation in maintaining appropriate translation of age-dependent transcripts. In a directed RNAi screen we identified the 18S rRNA N6’-dimethyl adenosine (m6,2A) methyltransferase, dimt-1, as a regulator of C. elegans lifespan and stress resistance. Lifespan extension induced by dimt-1 deficiency required a functional germline and the Rag GTPase, raga-1, which links amino acid sensing to mechanistic target of rapamycin (mTOR) complex (mTORC)1. Using an auxin-inducible degron tagged version of dimt-1 we demonstrate that DIMT-1 functions in the worms germline after mid-life to regulate lifespan. We further found that knock-down of dimt-1 leads to selective translation of transcripts important for stress resistance and lifespan regulation in the C. elegans germline in mid-life. Our findings highlight a new role for rRNA modifications such as m6,2A and ribosome heterogeneity more broadly, in maintaining appropriate translation later in life to promote healthy aging.
2024-06-06 | GSE237802 | GEO
Project description:DNA methylation profile of mouse sperm from conventionally-raised mice and gut dysbiosis experienced mice were characterized using whole-genome bisulfite sequencing. Genome-wide DNA methylation changes between control and dysbiotic male�s sperm were highly comparable, with no change in DNAme globally or at genomic features, only 21 differentially methylated regions (DMR) were identified, which did not overlap known regulatory elements. Epididymal sperm samples were harvested from 11 weeks old inbred male mice that were experiencing gut microbiota dysbiosis for 6-week (antibiotics treated, n=5), or drink sterilized water (control, n=5).
2023-11-13 | E-MTAB-10033 | biostudies-arrayexpress
Project description:Bacteria can circumvent the effect of antibiotics by transitioning to a poorly understood physiological state that does not involve conventional genetic elements of resistance. Here we examine antibiotic susceptibility with a Class A β-lactamase+ invasive strain of Klebsiella pneumoniae that was isolated from a lethal outbreak within laboratory colonies of Chlorocebus aethiops sabaeus monkeys. Bacterial responses to the ribosomal synthesis inhibitors streptomycin and doxycycline resulted in distinct proteomic adjustments that facilitated decreased susceptibility to each antibiotic. Drug-specific changes to proteomes included proteins for receptor-mediated membrane transport and sugar utilization, central metabolism, and capsule production, while mechanisms common to both antibiotics included elevated scavenging of reactive oxygen species and turnover of misfolded proteins. Resistance to combined antibiotics presented integrated adjustments to protein levels as well as unique drug-specific proteomic features. Our results demonstrate that dampening of Klebsiella pneumoniae susceptibility involves global remodeling of the bacterial proteome to counter the effects of antibiotics and stabilize growth.
2019-03-14 | PXD010244 | Pride
Project description:Mammalian species have co-evolved with intestinal microbial communities that can shape development and adapt to environmental changes, including antibiotic perturbation or nutrient flux. In humans, especially children, microbiota disruption is common, yet the dynamic microbiome recovery from early-life antibiotics is still uncharacterized. Using a mouse model mimicking pediatric antibiotic use, we found that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide altered both host and microbiota development. Early-life PAT accelerated total mass and bone growth, and resulted in progressive changes in gut microbiome diversity, population structure, and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. While control microbiota rapidly adapted to a change in diet, PAT slowed the ecological progression, with delays lasting several months in response to the macrolide. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment.
2015-05-07 | GSE68603 | GEO
Project description:Mammalian species have co-evolved with intestinal microbial communities that can shape development and adapt to environmental changes, including antibiotic perturbation or nutrient flux. In humans, especially children, microbiota disruption is common, yet the dynamic microbiome recovery from early-life antibiotics is still uncharacterized. Using a mouse model mimicking pediatric antibiotic use, we found that therapeutic-dose pulsed antibiotic treatment (PAT) with a beta-lactam or macrolide altered both host and microbiota development. Early-life PAT accelerated total mass and bone growth, and resulted in progressive changes in gut microbiome diversity, population structure, and metagenomic content, with microbiome effects dependent on the number of courses and class of antibiotic. While control microbiota rapidly adapted to a change in diet, PAT slowed the ecological progression, with delays lasting several months in response to the macrolide. This study identifies key markers of disturbance and recovery, which may help provide therapeutic targets for microbiota restoration following antibiotic treatment. C57BL/6J mice received three antibiotic courses: at days 10-15, 28-31, and 37-40 of life, amoxicillin or tylosin.Livers were collected at age 22 weeks, RNA was extracted, and transcriptional differences were measured by microarray analysis.
2015-05-07 | E-GEOD-68603 | biostudies-arrayexpress
Project description:Innate lymphoid cells (ILCs) play a critical role in maintaining intestinal health in homeostatic and diseased conditions. During C. difficile infection (CDI), IL-33 activates ILC2 to protect from colonic damage and mortality. The function of IL-33 and ILC is tightly regulated by the intestinal microbiota. We set out to determine the impact of antibiotic-induced disruption of the microbiome on ILC function. Our goal was to understand antibiotic-induced changes in ILC function on susceptibility to C. difficile colitis in a mouse model. We utilized high-throughput single-cell RNAseq to investigate the phenotypic features of colonic ILC at baseline, after antibiotic administration with or without IL-33 treatment. We identified a heterogeneous landscape of colonic ILCs with gene signatures of inflammatory, anti-inflammatory, migratory, progenitor, plastic, and antigen-presenting ILC. Antibiotic treatment decreased ILC2 while coordinately increasing ILC1 and ILC3 phenotypes. Notably, Ifng+, Ccl5+, and Il23r+ ILC increased after antibiotics. IL-33 treatment counteracted the antibiotic effect by downregulating ILC1 and ILC3 and activating ILC2. In addition, IL-33 treatment markedly induced the expression of type 2 genes, including Areg and Il5. Finally, we identified amphiregulin, produced by ILC2, as protective duringC. difficileinfection. Together, our data expand our understanding of how antibiotics induce susceptibility to C. difficile colitis through their impact on ILC subsets and function.
2024-02-04 | GSE254628 | GEO
Project description:A leading cause of morbidity and mortality during influenza infection is the development of a secondary bacterial pneumonia, which is appropriately treated with antibiotics. In the absence of a bacterial superinfection, prescribing antibiotics is not indicated but has nevertheless become a common clinical practice for those presenting with a respiratory viral illness. We found that antibiotic use during an antecedent influenza infection impaired the lung innate immunologic defenses toward a secondary challenge with methicillin-resistantStaphylococcus aureus(MRSA). The antibiotics perturbed the gut microbiome causing a fungal dysbiosis that drives an increase in lung eosinophils. We also demonstrate eosinophils, through the release of major basic protein, impair macrophage ability to clear MRSA. Moreover, we provide clinical evidence that eosinophils positively correlate with antibiotic use and worsened outcomes in patients hospitalized for viral infections. Altogether, our work establishes a counterproductive effect of antibiotic treatment during influenza infection that have negative immunologic consequences in the lungs thereby increasing the risk of developing a secondary bacterial infection.
2024-08-21 | GSE243542 | GEO
Project description:The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic down-regulation of insulin/insulin-like growth factor 1 (Igf1) signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2+/- mice to Ins2+/+ littermate controls, on a genetically stable Ins1-null background. Proteomic and transcriptomic analyses of livers from 25 week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2+/- mice. Halving Ins2 lowered circulating insulin by 25-34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance, and that limiting basal insulin levels can extend lifespan.
2017-07-07 | PXD006613 | Pride