Towards a mechanistic understanding of the role of gut microbiota in postnatal growth impairment
从机制上理解肠道微生物群在产后生长障碍中的作用
基本信息
- 批准号:10655393
- 负责人:
- 金额:$ 7.43万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-26 至 2025-09-25
- 项目状态:未结题
- 来源:
- 关键词:3 year oldAddressAgeAntibioticsAntimicrobial ResistanceBangladeshBifidobacteriumBioinformaticsBiologicalBloodBlood specimenCarbohydratesCharacteristicsChildChild HealthChildhoodClinicalClinical TrialsCompetenceDietDiseaseEndotoxinsEngineeringEnvironmental Risk FactorEtiologyFecesFellowshipFoodFoundationsFutureGastroenterologyGenesGenomeGenomicsGoalsGrowthHealthHumanHuman BiologyHuman MicrobiomeImmune responseImpairmentInflammationInflammatoryInflammatory ResponseInterventionIntestinal permeabilityIntestinesLifeLipidsMalnutritionMeasurementMediatingMentorshipMetabolicMetagenomicsMicrobeModelingMucosal Immune SystemMultiomic DataMusOutcomePathway interactionsPeriodicalsPermeabilityPhysiologicalProductionResearchResearch PersonnelRiskRoleRuralSamplingSanitationSiteSpecimenStatistical ModelsTaxonomyTrainingTransplantationVariantWorkcareercohortcommensal microbesdietary supplementsenteric pathogenexperiencegut inflammationgut microbesgut microbiomegut microbiotaimprovedin vivoinsightmetabolomicsmetagenomic sequencingmicrobialmicrobiotamouse modelnovelnutrient absorptionnutritional supplementationpostnatalprogramsrRNA Genesrational designreconstitutionresistance geneskillssmall moleculestatisticsstemsystemic inflammatory response
项目摘要
PROJECT SUMMARY
Precision engineering of the gut microbiota requires a mechanistic understanding of how microbes interact with
host physiological pathways in order to produce desired health outcomes. In stunted children, commensal gut
microbes have been correlated with aberrant host inflammation and growth impairment, but mechanisms
underlying these associations are poorly understood. Mouse models have suggested causality, but they fail to
recapitulate the dynamics of the mucosal immune system in humans and the complexity of the human gut
microbiota. This project will interrogate these questions in vivo in a cohort of >1500 children from rural
Bangladesh at risk for stunting, for which biological specimens were collected longitudinally from 0-3 years of
age. Preliminary analysis of 16S rRNA gene sequences from >3700 fecal samples collected from these children
has identified a Bifidobacterium sequence variant that is highly correlated with intestinal inflammation and
subsequent growth faltering. In Aim 1, I will identify strain-specific microbial genes that might mediate these
observed associations. In Aim 2, I will interrogate the mechanistic underpinnings by evaluating microbial small-
molecule metabolites in feces and blood associated with high levels of Bifidobacterium and concurrent gut and/or
systemic inflammation in children 14 months old. In Aim 3, I will use advanced latent variable statistical modeling
to determine the importance of associated groups of microbial (taxonomic, metagenomic, and metabolic) and
host (gut and systemic inflammation) features on future growth faltering. I will also estimate the maximum
achievable improvement in child growth from a theoretical, 100% efficacious microbiota-manipulation
intervention, providing an expected effect size for comparison with other intervention alternatives. This work will
increase our mechanistic understanding of the associations between early life gut microbiota and aberrant
intestinal/systemic inflammation as well as future growth faltering, producing new options for predictably
manipulating the gut microbiota to mitigate adverse health outcomes. The proposed project will provide a
rigorous training experience in the fields of gut microbiota, microbial metabolites, multivariate statistics, and
pediatric gastroenterology under the mentorship of a group of scientific experts, and will equip me with the skills
necessary to become an independent researcher.
项目摘要
肠道微生物群的精确工程需要对微生物如何与微生物相互作用的机制进行理解。
宿主生理途径,以产生期望的健康结果。在发育不良的儿童中,
微生物与异常的宿主炎症和生长障碍有关,
对这些关联的基础了解甚少。小鼠模型已经提出了因果关系,但他们没有
概括了人类粘膜免疫系统的动态和人类肠道的复杂性
微生物群本项目将在一个超过1500名来自农村的儿童队列中对这些问题进行活体调查。
孟加拉国有发育迟缓的风险,为此从0-3岁纵向收集生物标本,
年龄从这些儿童收集的>3700份粪便样品中初步分析16 S rRNA基因序列
已经鉴定出与肠道炎症高度相关的双歧杆菌序列变体,
随后的增长放缓。在目标1中,我将确定可能介导这些的菌株特异性微生物基因。
观察协会。在目标2中,我将通过评估微生物的小-
粪便和血液中与高水平双歧杆菌和并发肠道和/或
14个月大的儿童全身性炎症。在目标3中,我将使用高级潜变量统计建模
确定相关微生物组(分类、宏基因组和代谢)的重要性,
宿主(肠道和全身炎症)特征对未来生长的影响。我也会估计
通过理论上100%有效的微生物群控制,可实现儿童生长的改善
干预,提供与其他干预替代方案进行比较的预期效应量。这项工作将
增加我们对早期肠道菌群与异常肠道菌群之间关系的机械理解,
肠道/全身性炎症以及未来的增长步履蹒跚,产生新的选择,可预见的
操纵肠道微生物群以减轻不良健康后果。拟议项目将提供一个
在肠道微生物群,微生物代谢物,多元统计等领域的严格培训经验,
在一组科学专家的指导下,我将学习儿科胃肠病学,并将使我掌握
成为一名独立的研究员。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
JESSICA A. GREMBI其他文献
JESSICA A. GREMBI的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('JESSICA A. GREMBI', 18)}}的其他基金
Towards a mechanistic understanding of the role of gut microbiota in postnatal growth impairment
从机制上理解肠道微生物群在产后生长障碍中的作用
- 批准号:
10765586 - 财政年份:2022
- 资助金额:
$ 7.43万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 7.43万 - 项目类别:
Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 7.43万 - 项目类别:
Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 7.43万 - 项目类别:
Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 7.43万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 7.43万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 7.43万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 7.43万 - 项目类别:
EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 7.43万 - 项目类别:
Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 7.43万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 7.43万 - 项目类别:
Research Grant