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Mediation Analysis Methods to Model Human Microbiome Mediating Disease-Leading Causal Pathways in Children

用于模拟人类微生物组介导儿童疾病主导因果路径的中介分析方法

基本信息

批准号：
10228590
负责人：
Zhigang Li
金额：
$ 40.41万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10228590
关键词：
Accounting Address Antibiotics Arsenic Asthma Biological Biological Process Birth Child Child Health Childhood Clinical Cohort Studies Complex Complication Computer software Coupled Custom Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator Data Data Analyses Dependence Development Diet Disease Drug usage Epidemiology Foundations Funding Gene Mutation Genome Goals Growth Health High-Throughput Nucleotide Sequencing Human Human Microbiome Hypersensitivity Individual Infant Infection Inherited Life Literature Mediating Mediation Mediator of activation protein Medical Methodology Methods Microbe Modeling Molecular Mothers New Hampshire Newborn Infant Outcome Pathogenicity Pathway interactions Pattern Peptide Initiation Factors Performance Phylogenetic Analysis Play Population Pregnancy Research Research Personnel Role Sensitivity and Specificity Structure Taxonomy Technology Testing Toxic Environmental Substances Translational Research Translations Trees United States National Institutes of Health Validation Weight Gain atopy breast milk microbiome children with cystic fibrosis clinical practice design drinking water feeding gut microbiome high dimensionality human model infant gut microbiome innovation insight longitudinal dataset microbial microbiome microbiome alteration microbiome composition microbiome research microorganism mother nutrition novel perinatal period prenatal prenatal exposure simulation software development tool user friendly software user-friendly web app

项目摘要

Abstract Emerging evidence suggests that human microbiome, composed of collective genomes of as many as 100 trillion microorganisms, could be mediating disease-leading causal pathways initiated by environmental toxicants or other factors such as drug usage. Prenatal arsenic exposure through drinking water, for example, could initiate perturbation of gut microbiome, and therefore, children could inherit perturbed microbiome composition if their mothers have arsenic exposure during perinatal period. The unhealthy microbiome composition could, in turn, induce children’s asthma, infection and allergy which could explain that arsenic exposure during pregnancy is related to children’s infection. Taken together, arsenic exposure could be the initiation of causal pathways leading to children’s infection through perturbed mother’s microbiome being passed to children. There are many other possible initiation factors such as diet, gene mutation, delivery mode and antibiotics leading to different children’s health outcomes. These mediations could happen through changes in particular microbial taxa or though the perturbation of microbiome population structure. While high-throughput sequencing technologies can characterize the taxonomic composition of microbiome in unprecedented detail, none of the existing mediation analysis methods is adequate enough to model the mediation effects of microbiome due to the unique challenging features of microbiome data. Therefore, there is an urgent need to have appropriate mediation analysis methods in place for estimating and testing the mediational effects of human microbiome. To address these issues, we will develop two general mediation analysis frameworks to identify mediation through changes in individual microbial taxa and model mediation though the perturbation of overall microbiome composition. The models will be tested with extensive simulations and cross validations. An R package and an interactive web application will be developed for model implementations. In the real study applications, we will quantify and test the mediation effects of infant gut microbiome and breast-milk microbiome in the relations between prenatal exposures (e.g., arsenic exposure, maternal diet) and childhood infections and allerg/atopy in the first year of life using the rich data from the large ongoing longitudinal molecular epidemiologic New Hampshire Birth Cohort study. With the applications of the proposed models in a cystic fibrosis (CF) study, we will examine whether CF transmembrane conductance regulator gene mutations lay the biological foundation for patterns in the developing microbiome in the gut that are associated with CF exacerbation onset in newborn children with CF. By analyzing the data from the Infant Growth and Microbiome Study, we will answer the key question of the role played by gut microbiome in associating early antibiotic exposure, delivering mode and feeding mode with infant weight gain.

文摘

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Perceived Effectiveness of Medical Cannabis Among Adults with Chronic Pain: Findings from Interview Data in a Three-Month Pilot Study.

DOI：
10.26828/cannabis/2023/000149
发表时间：
2023
期刊：
Cannabis (Albuquerque, N.M.)
影响因子：
0
作者：
通讯作者：

What's in a Do-Not-Resuscitate Order? Understanding the Impact on Pre-arrest Life Support and Factors Influencing Misconceptions.

不复苏令包含哪些内容？

DOI：
10.1007/s11606-019-05431-7
发表时间：
2020
期刊：
Journal of general internal medicine
影响因子：
5.7
作者：
Charoonratana,VictoriaT;Stewart,Talia;Zhang,Runzhi;Li,Zhigang;DesBiens,MarthaT;Slogic,Scott;Vergo,MaxwellT
通讯作者：
Vergo,MaxwellT

Randomized Trial of a Palliative Care Intervention to Improve End-of-Life Care Discussions in Patients With Metastatic Breast Cancer.

姑息治疗干预措施的随机试验，以改善转移性乳腺癌患者的寿命末护理讨论。

DOI：
10.6004/jnccn.2021.7040
发表时间：
2022-03
期刊：
Journal of the National Comprehensive Cancer Network : JNCCN
影响因子：
0
作者：
Greer JA;Moy B;El-Jawahri A;Jackson VA;Kamdar M;Jacobsen J;Lindvall C;Shin JA;Rinaldi S;Carlson HA;Sousa A;Gallagher ER;Li Z;Moran S;Ruddy M;Anand MV;Carp JE;Temel JS
通讯作者：
Temel JS

Getting Creative: Pilot Study of a Coached Writing Intervention in Patients with Advanced Cancer at a Rural Academic Medical Center.

发挥创造力：在农村学术医疗中心对晚期癌症患者进行辅导写作干预的试点研究。