Metagenomics of the circulating blood microbiome and systemic inflammation in preterm infants

早产儿循环血液微生物组和全身炎症的宏基因组学

基本信息

批准号：
9894147
负责人：
Mohan Pammi
金额：
$ 8万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-04 至 2022-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9894147
关键词：
37 weeks gestation Actinobacteria class Adult Anti-Inflammatory Agents Antibiotics Bacteria Bacterial DNA Bacteroidetes Bioinformatics Blood Blood specimen Brain Injuries Bronchopulmonary Dysplasia Characteristics Clinical Core Facility DNA Data Disease Donor Selection Enrollment Evaluation Feces Firmicutes Functional disorder Human Human Volunteers Infant Infection Inflammation Inflammatory Injury Knowledge Lead Leukocytes Literature Liver diseases Lung Medical center Medicine Metadata Metagenomics Methods Neonatal Oral cavity Organism Outcome Patient-Focused Outcomes Patients Phylogenetic Analysis Plasma Population Premature Infant Proteobacteria Publishing Recombinant DNA Reporting Research Research Proposals Retinopathy of Prematurity Ribosomal RNA Role Route Science Sepsis Serum Shotgun Sequencing Skin Source Sterility Swab Symptoms Technical Expertise Technology Testing Texas Time Tissues Vagina Viral bacteriome base chemokine clinically relevant college cytokine gastrointestinal epithelium gut microbiome healthy volunteer improved innovation insight microbial microbiome microbiota multiple omics mycobiome neonatal outcome neonatal sepsis neonate novel novel strategies organ injury preterm newborn stool sample tissue injury tool virome

37 weeks gestation Actinobacteria class Adult Anti-Inflammatory Agents Antibiotics Bacteria Bacterial DNA Bacteroidetes Bioinformatics Blood Blood specimen Brain Injuries Bronchopulmonary Dysplasia Characteristics Clinical Core Facility DNA Data Disease Donor Selection Enrollment Evaluation Feces Firmicutes Functional disorder Human Human Volunteers Infant Infection Inflammation Inflammatory Injury Knowledge Lead Leukocytes Literature Liver diseases Lung Medical center Medicine Metadata Metagenomics Methods Neonatal Oral cavity Organism Outcome Patient-Focused Outcomes Patients Phylogenetic Analysis Plasma Population Premature Infant Proteobacteria Publishing Recombinant DNA Reporting Research Research Proposals Retinopathy of Prematurity Ribosomal RNA Role Route Science Sepsis Serum Shotgun Sequencing Skin Source Sterility Swab Symptoms Technical Expertise Technology Testing Texas Time Tissues Vagina Viral bacteriome base chemokine clinically relevant college cytokine gastrointestinal epithelium gut microbiome healthy volunteer improved innovation insight microbial microbiome microbiota multiple omics mycobiome neonatal outcome neonatal sepsis neonate novel novel strategies organ injury preterm newborn stool sample tissue injury tool virome

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项目摘要

PROJECT SUMMARY The sterility of circulating human blood has been questioned. A circulating blood microbiome in healthy and disease states have been reported in adults associated with systemic inflammation but no such data exists in preterm neonates. Our preliminary data shows that the blood of neonates whose blood cultures were negative and who were considered non-infected, contained microbial DNA that can be characterized into distinct phylogenetic groups. The hypothesis of the proposed research is that the microbial diversity and composition of the circulating blood microbiome in preterm neonates is altered in infective states such as sepsis, and the blood microbiome contributes to systemic inflammation. We will use a holistic, multi- omics approach to test our hypothesis using 2 specific aims. In specific aim 1, we will determine the microbial diversity and composition of the circulating blood microbiome (bacterial, fungal and viral) in healthy preterm neonates and compare it with infants with culture-positive and culture-negative sepsis. In our second specific aim, we propose to determine the association of the blood microbiome signatures with systemic inflammation and neonatal outcomes. Our study will enroll a total of 60 preterm neonates; 20 with culture-proven sepsis, 20 neonates who do not have sepsis but have blood cultures drawn for symptoms of sepsis and were negative and 20 asymptomatic preterm neonates. The bacterial microbiome will be evaluated by metagenomic whole shotgun sequencing, fungal microbiome (mycobiome) by targeting ITS2 region and virome by established methods. Stool and skin swabs will be evaluated by 16S rDNA sequencing and cytokines profiles in the serum will be evaluated. We will use multivariable analyses to correlate microbial load, diversity and composition and cytokine profiles to clinical outcomes. Our proposal is innovative in that the presence of the blood microbiome, it’s association with inflammation and outcomes in the neonatal population has not been reported and will challenge the current paradigm of sterile blood in healthy neonates. The significance of the proposed research is that we will underpin the pathophysiology of ‘culture-negative sepsis’ that is often associated with overuse of antibiotics. By utilizing our state-of-the-science technology, analysis tools and technical expertise available at the Texas Medical Center, we are poised to advance our knowledge on the blood microbiome and inflammatory injury, that may lead to innovative anti-inflammatory therapy in vulnerable preterm infants.

项目摘要循环人血的不育已受到质疑。健康和据报道，与全身感染相关的成年人已经报道了疾病状态，但没有此类数据早产新生儿。我们的初步数据表明，血液培养的新生儿的血液为阴性谁被认为是未感染的，含有微生物DNA，可以将其表征为不同系统发育群体。拟议研究的假设是微生物多样性和在感染性状态中，早产新生儿中循环血液微生物组的组成改变了作为败血症，血液微生物组有助于系统性炎症。我们将使用整体，多 OMICS使用2个特定目标检验我们的假设的方法。在特定目标1中，我们将确定微生物健康早产中循环血液微生物组（细菌，真菌和病毒）的多样性和组成新生儿并将其与具有培养阳性和培养阴性败血症的婴儿进行比较。在我们的第二个特定目的，我们建议确定血液微生物组特征与全身性炎症的关联和新生儿结果。我们的研究将招募60名早产新生儿。 20与培养败血症，20 没有败血症但有血液培养的新生儿因脓毒症的症状而绘制，并且是阴性的， 20个无症状早产。细菌微生物组将通过宏基因组全shot弹枪进行评估测序，真菌微生物组（Mycobiome）通过既定方法靶向ITS2区域和病毒群。凳子将通过16S rDNA测序评估皮肤拭子，并评估血清中的细胞因子谱。我们将使用多变量分析来将微生物负载，多样性和组成以及细胞因子曲线相关联临床结果。我们的建议具有创新性，因为血液微生物组的存在，它与尚未报告新生儿人群的炎症和结局，并将挑战当前健康新生儿中无菌血液的范式。拟议的研究的重要性是我们将支持通常与抗生素过度使用有关的“培养阴性败血症”的病理生理学。通过使用我们的最先进技术，分析工具和技术专长，可在德克萨斯州医疗中心提供我们被中毒以提高我们对血液微生物组和炎症性损伤的了解，这可能导致脆弱的早产儿的创新抗炎疗法。