Metabolic And Spatial Competition For Dietary Fiber Between Commensal And Pathogenic Gut Microbes
共生肠道微生物和致病肠道微生物之间膳食纤维的代谢和空间竞争
基本信息
- 批准号:10327331
- 负责人:
- 金额:$ 16.22万
- 依托单位:
- 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:2020-04-01 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:AdhesionsAdhesivesBacteriaBacterial AdhesionBacteroidesBar CodesBindingBiological AssayCarbohydratesCarbonCecumCell AdhesionCellsCollectionCommunitiesConsumptionDatabasesDiarrheaDietDietary CarbohydratesDietary ComponentDietary FiberDietary InterventionDiseaseEnteralEpithelialEscherichia coliFiberFoodGenesGnotobioticGoalsGrowthHarvestHealthHomeostasisHumanImmuneIn SituIncubatedIndividualInfectionInterventionIntestinesKnock-outKnowledgeLactobacillusLibrariesMeasuresMediatingMetabolicMetabolismMicrobeMicrobial GeneticsModelingMusNitrogenNutrientOrganismOutcomePathogenicityPlantsPolysaccharidesPreparationProbioticsProteobacteriaProteomicsPsylliumResearchResourcesSamplingSurfaceTestingUrinary tract infectionUropathogenic E. coliWorkbasebeneficial microorganismcommensal microbesdesigndietaryenteric infectionexperimental studyfitnessgenetic analysisgut colonizationgut microbesgut microbiotain vivoinsightinterestmagnetic beadsmembermicrobial communitymicrobiotamutantparticlepathogenpathogenic Escherichia colipathogenic microbeprebioticsresponsetherapy designtool
项目摘要
PROJECT SUMMARY
The microbial community that resides in the human intestine profoundly influences host metabolism, immune
homeostasis, and the outcome of enteric infections. Dietary fiber is a promising tool for manipulating the gut
microbiota to promote organisms that provide beneficial functions to the host. Though, it is currently difficult to
predict which gut bacterial species will respond to fiber-based dietary interventions, interspecies competition
makes it possible to precisely target beneficial species of interest using a particular fiber type. Bacterial species
with pathogenic potential, such as uropathogenic E. coli (UPEC), are present in the gut microbiota of
asymptomatic individuals and these species have the capacity to expand in response to fiber. Exploiting
competition between pathogens and their non-pathogenic relatives to reduce pathogen load in the gut will
require detailed knowledge of the genes underlying these species’ overlapping nutrient harvesting strategies,
including genes mediating adhesion to nutrient-rich diet-derived particles. The following aims will test the
hypotheses that (i) expansion of commensal E. coli in the gut in response to dietary fiber can reduce the fitness
of pathogenic E. coli, and that (ii) commensal and pathogenic bacterial species compete for adhesion to the
same diet-derived surfaces in the intestinal lumen. In Aim1, I will identify dietary fibers that selectively increase
the abundance of commensal E. coli in vivo. Preliminary studies have identified a widely consumed fiber that
increases the abundance of commensal E. coli in a model microbial community. I will define the mechanism of
action by colonizing these mice with an E. coli transposon mutant library and performing community-wide
quantitative proteomics and forward genetic analyses. To model a gut reservoir of pathogenic E. coli, I will
substitute UPEC for commensal E. coli in this community, and then administer commensal E. coli with or
without fiber to identify interventions that reduce UPEC abundance. In Aim2, I will determine whether
commensal and pathogenic microbes adhere to the same surfaces in the gut. A multiplex adhesion assay,
using glycan-coated magnetic beads, identified dietary fibers that support adhesion of both UPEC and
commensal E. coli. I will validate adhesive interactions in vivo by administering these particles to mice and
measuring bacterial localization around beads in situ. Application of the bead-based adhesion assay to cecal
microbiota of mice colonized with uncultured human fecal samples will identify additional E. coli strains, as well
as uncharacterized gut microbes, that adhere to dietary glycans in vivo. This research will (i) provide insights
into the ecological relationships that determine the outcome of dietary interventions designed to promote
beneficial species at the expense of known pathogens and ii) provide candidate dietary components, bacterial
strains, and microbial genetic targets for manipulating these relationships to enhance human health.
项目摘要
驻留在人体肠道中的微生物群落深刻地影响着宿主的新陈代谢、免疫功能和免疫功能。
体内平衡和肠道感染的结果。膳食纤维是一种很有前途的操纵肠道的工具
微生物群,以促进为宿主提供有益功能的生物体。然而,目前很难
预测哪些肠道细菌物种将对基于纤维的饮食干预、种间竞争
使得可以使用特定的纤维类型精确地靶向感兴趣的有益物种。细菌物种
具有致病潜力的菌株,如尿路致病性E.大肠杆菌(UPEC),存在于肠道微生物群中,
无症状的个体,并且这些物种具有响应于纤维而扩展的能力。利用
病原体和它们的非病原性亲属之间为减少肠道中的病原体负荷而进行的竞争将
需要详细了解这些物种重叠的营养收获策略背后的基因,
包括介导对富含营养的饮食来源的颗粒的粘附的基因。以下目标将检验
假设(i)共生E.大肠杆菌在肠道中对膳食纤维的反应可以降低健身
致病性大肠大肠杆菌,和(ii)真菌和致病细菌物种竞争粘附到
在肠腔中具有相同的饮食来源的表面。在目标1中,我将确定选择性增加的膳食纤维
Escherosal E. coli中的表达。初步研究已经确定了一种广泛消费的纤维,
增加了E.大肠杆菌在一个模型微生物群落。我将定义
通过用E.大肠杆菌转座子突变体库和执行社区范围内
定量蛋白质组学和正向遗传分析。为了模拟致病性大肠杆菌的肠道储库。大肠杆菌,我会
用UPEC代替Escherosal E.大肠杆菌,然后在该社区中,大肠杆菌,或
没有纤维来确定减少UPEC丰度的干预措施。在目标2中,我将确定是否
肠道微生物和病原微生物粘附在肠道的同一表面。多重粘附测定,
使用聚糖包被的磁珠,确定了支持UPEC和
阿格萨尔湖杆菌我将通过给小鼠施用这些颗粒来验证体内粘附相互作用,
原位测量珠周围的细菌定位。微珠粘附试验在盲肠中的应用
用未培养的人粪便样品定殖的小鼠的微生物群将鉴定额外的E.大肠杆菌菌株,
作为未表征的肠道微生物,其在体内粘附于膳食聚糖。该研究将(i)提供见解
进入生态关系,决定饮食干预的结果,旨在促进
有益的物种,以已知的病原体为代价,和ii)提供候选的膳食组分,细菌
菌株和微生物遗传靶标,用于操纵这些关系以增强人类健康。
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)
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{{ truncateString('Michael L Patnode', 18)}}的其他基金
Spatially Organized Bacterial Interaction Networks in the Gut Microbiota
肠道微生物群中空间组织的细菌相互作用网络
- 批准号:
10715436 - 财政年份:2023
- 资助金额:
$ 16.22万 - 项目类别:
Metabolic And Spatial Competition For Dietary Fiber Between Commensal And Pathogenic Gut Microbes
共生肠道微生物和致病肠道微生物之间膳食纤维的代谢和空间竞争
- 批准号:
10132316 - 财政年份:2020
- 资助金额:
$ 16.22万 - 项目类别:
Metabolic And Spatial Competition For Dietary Fiber Between Commensal And Pathogenic Gut Microbes
共生肠道微生物和致病肠道微生物之间膳食纤维的代谢和空间竞争
- 批准号:
10545761 - 财政年份:2020
- 资助金额:
$ 16.22万 - 项目类别:
Mechanisms for Selective Modulation of Beneficial Human Gut Microbes by Specific Dietary Plant Polysaccharides
特定膳食植物多糖选择性调节有益人类肠道微生物的机制
- 批准号:
9124214 - 财政年份:2016
- 资助金额:
$ 16.22万 - 项目类别:
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