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Population Genomic Analysis of Gut Microbial Colonization in Premature Infants

早产儿肠道微生物定植的群体基因组分析

基本信息

批准号：
10663304
负责人：
Jillian Banfield
金额：
$ 77.23万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-15 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10663304
关键词：
16S ribosomal RNA sequencing Adverse effects Aerobic Agreement Ampicillin Anaerobic Bacteria Ancillary Study Animals Antibiotic Resistance Antibiotic Therapy Antibiotics Antimicrobial Resistance Bacteria Bacterial Antibiotic Resistance Bacterial Chromosomes Bacterial Genes Bacteriophages Biology Birth Blinded Cell Respiration Cessation of life Childhood Clinical Clinical Trials Collection Drug resistance Early Diagnosis Ecosystem Elements Enrollment Equipment and supply inventories Exposure to Face Formates Funding Genes Genetic Induction Genomics Gentamicins Gestational Age Grant Health Hospitals Hour Human Human Milk Incidence Infant Intestines Intravenous Knowledge Length Life Link Literature Longitudinal Studies Measures Metabolism Metagenomics Mobile Genetic Elements Mothers Multicenter Trials Mutation Necrotizing Enterocolitis Neonatal Newborn Infant Nitrogen Organism Outcome Outcome Study Oxidation-Reduction Oxygen Participant Patients Pattern Perinatal Placebo Control Placebos Plasmids Population Premature Infant Process Protocols documentation Randomized Rectum Reproduction Research Resistance Resolution Ribosomal RNA Saline Sampling Sampling Studies Sepsis Study Subject Swab Testing Time Time Series Analysis United States National Institutes of Health Vagina Variant Vertical Transmission adverse outcome antenatal clinically relevant early onset fitness gut health gut microbiome human data infant gut microbiome inter-individual variation knock-down late onset sepsis maternal microbiome member microbial microbial colonization microbiome microbiome analysis microbiome research microbiota novel opportunistic pathogen pathogen placebo group preterm newborn primary endpoint randomized placebo controlled trial rectal resistance gene resistant strain sex standard of care transcriptomics

项目摘要

Abstract A large body of literature now indicates that antenatal and neonatal antibiotic exposure is associated with adverse childhood outcomes due to disruption of the developing microbiome. In premature infants, the standard of care for many decades has included the administration of broad-spectrum antibiotics in the first hours of life as treatment for a presumptive diagnosis of early onset sepsis. However, nearly all preterm infants receiving these antibiotics do not actually have sepsis. This grant renewal application proposes an ancillary microbiome study linked to the NANO (NICU Antibiotics and Outcomes) Trial, a recently launched clinical trial that will challenge this longstanding practice of immediately prescribing antibiotics to newborn preterm infants. NANO will test the hypothesis that antibiotics at birth worsens outcomes in preterm infants that are clinically stable. This multicenter trial, which is led by members of our research team, will randomize 802 premature infants to receive intravenous ampicillin and gentamicin or a saline placebo control. The study will measure the impact of variables including mode of delivery, gestational age, sex, and receipt of maternal milk, and administration of maternal antepartum antibiotics. Infant fecal samples in the first month of life as well as maternal fecal and vaginal swabs will be collected in NANO for basic microbiome profiling in the antibiotics and placebo groups using 16S rRNA gene sequencing. Here, we propose to augment microbiome analyses of NANO study subjects using novel strain-level metagenomic strategies and by analyzing samples beyond the first month of life. With this strategy, we propose to Aim 1. Test the hypothesis that empiric antibiotics (EA) disrupts mother-infant strain sharing in preterm infants. Aim 2. Test the hypothesis that EA increases the abundance of gut bacterial antimicrobial resistance genes in preterm infants. Aim 3. Test the hypothesis that EA delays the transition from a gut ecosystem dominated by facultative anaerobes to one dominated by obligate anaerobes. Because NANO is a first-of-its-kind clinical trial evaluating antibiotic therapy during the first days of life, this ancillary study will provide a rare opportunity to ask and answer a unique set of questions about the biology of early gut bacterial colonization.

摘要

项目成果

期刊论文数量（25）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Infant gut strain persistence is associated with maternal origin, phylogeny, and traits including surface adhesion and iron acquisition.

DOI：
10.1016/j.xcrm.2021.100393
发表时间：
2021-09-21
期刊：
Cell reports. Medicine
影响因子：
0
作者：
Lou YC;Olm MR;Diamond S;Crits-Christoph A;Firek BA;Baker R;Morowitz MJ;Banfield JF
通讯作者：
Banfield JF

DOI：
10.1016/j.isci.2021.102875
发表时间：
2021-08-20
期刊：
iScience
影响因子：
5.8
作者：
Crisci MA;Chen LX;Devoto AE;Borges AL;Bordin N;Sachdeva R;Tett A;Sharrar AM;Segata N;Debenedetti F;Bailey M;Burt R;Wood RM;Rowden LJ;Corsini PM;van Winden S;Holmes MA;Lei S;Banfield JF;Santini JM
通讯作者：
Santini JM

Infant microbiome cultivation and metagenomic analysis reveal Bifidobacterium 2'-fucosyllactose utilization can be facilitated by coexisting species.

DOI：
10.1038/s41467-023-43279-y
发表时间：
2023-11-16
期刊：
Nature communications
影响因子：
16.6
作者：
Lou YC;Rubin BE;Schoelmerich MC;DiMarco KS;Borges AL;Rovinsky R;Song L;Doudna JA;Banfield JF
通讯作者：
Banfield JF

The developing premature infant gut microbiome is a major factor shaping the microbiome of neonatal intensive care unit rooms.

DOI：
10.1186/s40168-018-0493-5
发表时间：
2018-06-20
期刊：
Microbiome
影响因子：
15.5
作者：
Brooks B;Olm MR;Firek BA;Baker R;Geller-McGrath D;Reimer SR;Soenjoyo KR;Yip JS;Dahan D;Thomas BC;Morowitz MJ;Banfield JF
通讯作者：
Banfield JF

Widespread stop-codon recoding in bacteriophages may regulate translation of lytic genes.