Ontology highlight
ABSTRACT:
PROVIDER: PRJNA933769 | ENA |
REPOSITORIES: ENA
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Project description:<p class='ql-align-justify'>The gut microbiome has been associated with pathological neurophysiological evolvement in extremely premature infants suffering from brain injury. The exact underlying mechanism and its associated metabolic signatures in infants are not fully understood. To decipher metabolite profiles linked to neonatal brain injury, we investigated the longitudinal fecal and plasma metabolome of 51 extremely premature infants using LC-HRMS-based untargeted metabolomics. This was expanded by an investigation of bile acids and amidated bile acid conjugates in feces and plasma by LC-MS/MS-based targeted metabolomics. The resulting data was integrated with 16S rRNA gene amplicon gut microbiome profiles as well as patient cytokine, growth factor and T-cell profiles. We identified an early onset of differentiation in neuroactive metabolites and bile acids between infants with and without brain injury. We detected several bacterially-derived bile acid amino acid conjugates and secondary bile acids in the plasma already 3 days after delivery, indicating the early establishment of a metabolically active gut microbiome. These results give new insights into the early life metabolome of extremely premature infants.</p>
2023-12-30 | MTBLS7560 | MetaboLights
Project description:Extremely premature birth is associated with an increased risk for hypoxic brain injury due to lung immaturity and this results in severe long-term neurodevelopmental impairments. The susceptible cell types in the cerebral cortex at this critical developmental time point and the molecular mechanisms underlying associated gray matter defects in premature infants are not known. Here, we used a human three-dimensional (3D) cellular system to study the effect of changes in oxygen tension on the mid-gestation human cerebral cortex. We identified specific defects in intermediate progenitors, a cortical cell type associated with the expansion of the human cerebral cortex, and show that these are related to the unfolded protein response (UPR) and cell cycle changes. Moreover, we verify these findings in human primary cortical tissue and demonstrate that a modulator of the UPR pathway can prevent the reduction in intermediate progenitors following hypoxia. We anticipate that this human cellular platform will be useful in studying other environmental and genetic factors underlying brain injury in premature infants. We investigated the transcriptional changes associated with exposure to <1% O2 by performing RNA sequencing.
2019-03-05 | GSE112137 | GEO
Project description:<p><b>Public health importance</b>: Babies born preterm, approximately 1 out of every 9 live births in the United States, have significant respiratory morbidity over the first two years of life, exacerbated by respiratory viral infections. Many (<50%) return to pediatricians, emergency rooms and pulmonologists with symptoms of respiratory dysfunction (SRD): intermittent or chronic wheezing, poor growth and an excess of upper and lower respiratory tract infections (LRTI). SRD correlate inversely with gestational age and weight at birth and is more common in those with chronic lung disease of prematurity, yet its incidence and severity varies widely among both the prematurely born and those born at term. There is evidence from clinical studies and animal models that risks of LRTI and recurrent wheezing is influenced by gut and respiratory flora and by T cell responses to infection. Information gained from this study will be used to identify characteristics, risk factors and potential mechanisms for early and persistent lung disease in children born at term and born preterm.</p> <p>This Clinical Research Study will investigate the relationships between sequential respiratory viral infections, patterns of intestinal and respiratory bacterial colonization, and adaptive cellular immune phenotypes which are associated with increased susceptibility to respiratory infections and long term respiratory morbidity in preterm and full term infants. We hypothesize that the timing and acquisition of specific viral infections and bacterial species are directly related to respiratory morbidity in the first year of life as defined by SRD and by measures of pulmonary function. We hypothesize that cellular and molecular immuno-maturity are altered due to factors presented by premature birth in such a way as to promote chronic inflammatory and cytotoxic damage to the lung, with subsequent enhanced, damaging responses to infectious agents and environmental irritants. Our preliminary studies demonstrate both feasibility and expertise in mutiparameter immunophenotyping of small volume peripheral blood samples obtained from premature infants including gene expression arrays of flow cytometry sorted cells. We will use new technologies for known viral identification, as well as high-throughput metagenome sequencing of RNA and DNA virus like particles (VLP) to be used for viral discovery in infant respiratory sample and use of high-throughput pyrosequencing (454T) of bacterial 16S rRNA to determine shifts in bacterial community structure, occurring in pre-term (PT) as compared to full term (FT) infants, over the first year of life. Finally, we present statistical approaches to stratify disease risk predictors using multivariate logistic regression modeling approaches. We propose to evaluate T cell phenotypic and functional profiles relative to viral and predominant bacterial exposures according to highly complementary, but independent, Specific Objectives.</p> <p><b>Objective 1</b>: To determine if viral respiratory infections and patterns of respiratory and gut bacterial community structure (microbiome) in prematurely born babies predict the rate and degree of immunologic maturation, and pulmonary dysfunction, measured from birth to 36 weeks corrected gestational age (CGA).</p> <p><b>Objective 2</b>: To determine the relationship between respiratory viral infections and disease severity up to one year CGA, and the lymphocyte (Lc) phenotypes documented at term gestation (birth for term infants and 36 wks/NICU discharge in preterm infants) and at one year CGA. Three secondary outcomes of this objective will be to a) relate the quantity, type and severity of viral infections with pulmonary function at one and three years of life, b) relate the viral community structure to severity of viral infections and c) to seek evidence of modulation of viral susceptibility by bacterial respiratory and gut community structure (microbiome). The relationship of colonization with known and non-identified bacterial species in both the respiratory tract and the gut will be evaluated. </p>
| phs001347 | dbGaP
Project description:Colonizing commensal bacteria after birth are required for the proper development of the gastrointestinal tract. It is believed that bacterial colonization pattern in neonatal gut affects gut barrier function and immune system maturation. Studies on the development of faecal flora microbiota in infants on various formula feeds showed that the neonatal gut was first colonized with enterococci followed by other flora microbiota such as Bifidobacterium in breast feeding infants. Intriguingly, Bjorksten group Other studies showed that Bbabies who developed allergy were less often colonized with Enterococcus during the first month of life as compared to healthy infants. A lot of Many studies have been done on conducted to elucidate how bifidobacteria or lactobacilli, some of which are considered probiotic, regulate infant gut immunity. However, much fewer studies have been focused on enterococi. In our study, we demonstrate that E. faecalis, isolated from healthy newborns, suppress inflammatory responses activated in vivo and in vitro. We found E. faecalis attenuates proinflammatory cytokine secretions, especially IL-8, through JNK and p38 signaling pathways. This finding shed light on how the first colonizer, E.faecalis, regulate inflammatory responses in the host. Samples are analysed using web-based GEArray Expression Analysis Suite
2014-04-04 | E-GEOD-56485 | biostudies-arrayexpress
Project description:Periventricular white matter damage (PWMD) is the principal pathological type of brain damage in premature. It causes irreversible damage to the overall function of the central nervous system resulting in cerebral palsy, convulsions, epilepsy, cognitive, motor dysfunction and other late effects. CircRNAs are participate in the biological processes underlying many nervous system diseases. However, the circRNA expression profile of peripheral venous blood of premature infants with PWMD is not completely understood. Three premature with white matter damage (PWMD group) and three infants without brain injury (Normal group) were enrolled. Peripheral venous blood was collected from both groups for extraction of RNA and circRNA sequencing was performed. The RNA-seq technique was used to screen the differentially expressed circRNA in peripheral blood of infants with PWMD. The accuracy of sequencing results was verified by quantitative reverse transcription polymerase chain reaction (q-PCR) to the differentially express partial circRNA in the sequencing results. Bioinformatics analysis of Host genes was performed with differential circRNA. TargetScan and Miranda were used to predict circRNA-binding miRNAs and mapped into a circRNA-miRNA co-expression network. There were 119 significantly different circRNAs as compared with premature without brain injury, along with 1 circRNA was up-regulated and 4 circRNAs were down-regulated expression in the PWMD group. Combined with the existing research results and bioinformatics analysis results after sequencing, it is suggested that circRNA may regulate the occurrence and development of white matter damage in premature infants by interacting with miRNA. This first study of its kind further identified the expression profile of circRNA in peripheral blood of premature with WMD, and provide a novel targets for further investigation about the molecular mechanisms underlying PWMD and potential therapeutic intervention.
2020-05-20 | GSE131475 | GEO
Project description:Colonizing commensal bacteria after birth are required for the proper development of the gastrointestinal tract. It is believed that bacterial colonization pattern in neonatal gut affects gut barrier function and immune system maturation. Studies on the development of faecal flora microbiota in infants on various formula feeds showed that the neonatal gut was first colonized with enterococci followed by other flora microbiota such as Bifidobacterium in breast feeding infants. Intriguingly, Bjorksten group Other studies showed that Bbabies who developed allergy were less often colonized with Enterococcus during the first month of life as compared to healthy infants. A lot of Many studies have been done on conducted to elucidate how bifidobacteria or lactobacilli, some of which are considered probiotic, regulate infant gut immunity. However, much fewer studies have been focused on enterococi. In our study, we demonstrate that E. faecalis, isolated from healthy newborns, suppress inflammatory responses activated in vivo and in vitro. We found E. faecalis attenuates proinflammatory cytokine secretions, especially IL-8, through JNK and p38 signaling pathways. This finding shed light on how the first colonizer, E.faecalis, regulate inflammatory responses in the host.
2014-04-04 | GSE56485 | GEO
Project description:Neuropathic pain is an apparently spontaneous experience triggered by abnormal physiology of the peripheral or central nervous system, which evolves with time. Neuropathic pain arising from peripheral nerve injury is characterized by a combination of spontaneous pain, hyperalgesia and allodynia. There is no evidence of this type of pain in human infants or rat pups; brachial plexus avulsion, which causes intense neuropathic pain in adults, is not painful when the injury is sustained at birth. Since infants are capable of nociception from before birth and display both acute and chronic inflammatory pain behaviour from an early neonatal age, it appears that the mechanisms underlying neuropathic pain are differentially regulated over a prolonged postnatal period. We used microarrays to detail the global programme of gene expression underlying the differences in nerve injury between along the postnatal development and identified distinct classes of regulated genes during the injury Experiment Overall Design: We have performed a microarray analysis of the rat L4/L5 dorsal root ganglia, 7 days post spared nerve injury, a model of neuropathic pain. Genes that are regulated in adult rats displaying neuropathic behaviour were compared to those regulated in young rats (10 days old) that did not show the same neuropathic behaviour.
2010-01-30 | E-GEOD-15041 | biostudies-arrayexpress