Microbiota and Allergic Asthma Precision Prevention (MAAP2)
微生物群与过敏性哮喘精准预防 (MAAP2)
基本信息
- 批准号:10480057
- 负责人:
- 金额:$ 299.46万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-07-06 至 2025-08-31
- 项目状态:未结题
- 来源:
- 关键词:10 year old2 year oldAddressAdultAffectAge-MonthsAllergensAllergicAllergic DiseaseAllergic inflammationAsthmaBacteriaBirthBone MarrowBreast FeedingCanis familiarisCharacteristicsChildChildhoodChildhood AsthmaCollectionCommunitiesCommunity DevelopmentsConsensusDendritic CellsDevelopmentDietary FactorsDustEnvironmentEnvironmental ExposureEnvironmental Risk FactorExhibitsExposure toExtrinsic asthmaFecesFemaleFoodFoundationsGastrointestinal tract structureGoalsHealthHomeHouse DustHumanHuman MilkHypersensitivityIgEImmuneImmune systemIncidenceInfantInfant DevelopmentInflammationInhalant dose formInterventionJointsLactobacillusLifeLymphocyteMaternal ExposureMetabolicMicrobeMothersMusNewborn InfantOral AdministrationOrganismPartner in relationshipPatternPhenotypePopulationPregnancyPregnant WomenPrevalencePreventionPreventivePrimary PreventionPulmonary InflammationRegulatory T-LymphocyteResearchRespiratory Syncytial Virus InfectionsRespiratory syncytial virusRiskSerumShotgunsSkinSourceSpecimenSystems DevelopmentTimeUnited StatesVaginaVaginal delivery procedureVirusWorkbasecase controlcohortdesignfeedinggastrointestinalgene functiongut microbesgut microbiotahigh riskin uteroin vitro Assayindividualized preventionlifestyle factorsmaternal microbiotametabolic profilemetagenomic sequencingmicrobialmicrobial communitymicrobial compositionmicrobiotamicrobiota profilesmouse modelneonateoffspringoral supplementationpet animalprenatalpreventprotective effectpupsucklingvaginal microbiota
项目摘要
This application builds on the findings of our initial P01 designed to examine relationships between
environmental factors, especially pets, the infant gut microbiota and pediatric allergic asthma. We have shown
that: 1) dogs alter the microbial composition of dust in homes, 2) children born into homes with dogs have
different developmental patterns of gut microbiota and of IgE, 3) a distinct pattern of gut microbial composition
at 1 month of age is related to heightened risk of sensitization to multiple allergens at 2 years and of asthma at
4 years, and this pattern is influenced by numerous maternal characteristics, 4) sensitization to multiple food
and inhalant allergens at 2 years is strongly related to asthma at 10 years, 5) the metabolic profiles of stools
are related to later allergic sensitization 6) 12,13-DiHOME, a metabolite in stool, promotes development of Th2
lymphocytes and lowers development of Treg lymphocytes in an in vitro assay, and 7) in another study, the
meconial microbiota is distinct in neonates born to mothers with asthma. Our complementary mouse studies
have shown that: 1) gavaging with dust from homes with dogs reduces lung inflammation from allergen
sensitization and from respiratory syncytial virus (RSV) infection, 2) dog dust gavaged mice have increases in
Lactobacillus johnsonii in their ceca 3) oral administration of live L. johnsonii confers protection against
pulmonary inflammation induced by allergen and RSV, 4) L. johnsonii alters the function of bone marrow-
derived dendritic cells, 5) mice orally supplemented with L. johnsonii have altered serum metabolic profiles,
and 6) mouse pups born to L. johnsonii-supplemented mothers are protected against allergen challenge and
RSV infection. Collectively these findings showing the influence of maternal factors provide the basis for this
application's focus on the maternal gut and vaginal microbiotas during pregnancy, and how these relate to
infant gut microbial development and risk of allergic asthma. Project 1 focuses on the relationship of maternal
environmental and dietary factors, including maternal and infant gut microbiotas, to the child's developing a
high-risk for asthma phenotype by age 2 years. Project 2 proposes a detailed examination of relationships
between maternal and child microbiota, breast milk composition and IgE development amongst a cohort of
pregnancies in which the mother has current allergic asthma. Project 3 synergistically interacts with Projects 1
& 2 and also uses specimens from 10-year-old allergic asthma cases and controls in the initial P01 birth cohort
to examine gut microbes producing metabolites associated with a lowered risk of allergic inflammation and how
they are transferred from mother and established in offspring. Project 4 will use mouse models to examine the
relationships between manipulation of maternal microbiota and immune development in offspring. We
anticipate that together these studies will show that interventions directed at the gut microbiota of mothers
during pregnancy and of high-risk neonates after birth could reduce the risk of allergic asthma in childhood.
Such findings would provide the foundations of a rational strategy to prevent allergic asthma.
该应用程序建立在我们最初的 P01 的研究结果之上,旨在检查之间的关系
环境因素,尤其是宠物、婴儿肠道微生物群和小儿过敏性哮喘。我们已经展示了
1) 狗改变了家里灰尘的微生物成分,2) 出生在有狗的家庭中的孩子
肠道微生物群和 IgE 的不同发育模式,3) 肠道微生物组成的独特模式
1 个月大时的过敏反应与 2 岁时对多种过敏原过敏的风险增加以及 2 岁时患哮喘的风险增加有关。
4 年,这种模式受到许多母亲特征的影响,4)对多种食物的敏感性
2 岁时的吸入性过敏原与 10 岁时的哮喘密切相关,5) 粪便的代谢特征
与后来的过敏致敏有关 6) 12,13-DiHOME,粪便中的代谢物,促进 Th2 的发育
淋巴细胞并在体外测定中降低 Treg 淋巴细胞的发育,7) 在另一项研究中,
患有哮喘的母亲所生的新生儿的胎粪微生物群是独特的。我们的补充小鼠研究
研究表明:1)用狗家里的灰尘灌胃可以减少过敏原引起的肺部炎症
致敏和呼吸道合胞病毒 (RSV) 感染,2) 饲喂狗尘的小鼠的
盲肠中的约氏乳杆菌 3) 口服活约氏乳杆菌可以预防
过敏原和 RSV 诱导的肺部炎症,4) 约氏乳杆菌改变骨髓功能
衍生的树突状细胞,5) 口服补充约氏乳杆菌的小鼠的血清代谢谱发生了改变,
6) 补充了约氏乳杆菌的母亲所生的小鼠幼崽可以免受过敏原的挑战,并且
RSV 感染。总的来说,这些显示母亲因素影响的研究结果为这一点提供了基础
该应用程序的重点是怀孕期间母体肠道和阴道微生物群,以及它们与
婴儿肠道微生物发育和过敏性哮喘的风险。项目1关注母子关系
环境和饮食因素,包括母体和婴儿肠道微生物群,对孩子的发育有影响
2 岁时出现哮喘表型的高风险。项目2建议对关系进行详细检查
一组母婴微生物群、母乳成分和 IgE 发育之间的关系
母亲目前患有过敏性哮喘的怀孕。项目 3 与项目 1 协同互动
& 2 还使用了最初 P01 出生队列中 10 岁过敏性哮喘病例和对照的样本
检查产生与降低过敏性炎症风险相关的代谢物的肠道微生物以及如何
它们是从母亲那里转移过来并在后代中建立的。项目 4 将使用小鼠模型来检查
母体微生物群调控与后代免疫发育之间的关系。我们
预计这些研究将表明针对母亲肠道微生物群的干预措施
怀孕期间和出生后的高危新生儿可以降低儿童时期过敏性哮喘的风险。
这些发现将为预防过敏性哮喘的合理策略奠定基础。
项目成果
期刊论文数量(76)
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 bacterial community composition and food-related manifestation of atopy in early childhood.
- DOI:10.1111/pai.13704
- 发表时间:2022-01
- 期刊:
- 影响因子:4.4
- 作者:Joseph, Christine L. M.;Sitarik, Alexandra R.;Kim, Haejin;Huffnagle, Gary;Fujimura, Kei;Yong, Germaine Jia Min;Levin, Albert M.;Zoratti, Edward;Lynch, Susan;Ownby, Dennis R.;Lukacs, Nicholas W.;Davidson, Brent;Barone, Charles;Cole Johnson, Christine
- 通讯作者:Cole Johnson, Christine
Lactobacillus johnsonii supplementation attenuates respiratory viral infection via metabolic reprogramming and immune cell modulation.
- DOI:10.1038/mi.2017.13
- 发表时间:2017-11
- 期刊:
- 影响因子:8
- 作者:Fonseca W;Lucey K;Jang S;Fujimura KE;Rasky A;Ting HA;Petersen J;Johnson CC;Boushey HA;Zoratti E;Ownby DR;Levine AM;Bobbit KR;Lynch SV;Lukacs NW
- 通讯作者:Lukacs NW
Sex-associated early-life viral innate immune response is transcriptionally associated with chromatin remodeling of type-I IFN-inducible genes.
- DOI:10.1016/j.mucimm.2023.06.002
- 发表时间:2023-10
- 期刊:
- 影响因子:8
- 作者:Malinczak, Carrie-Anne;Fonseca, Wendy;Mire, Mohamed M.;Parolia, Abhijit;Chinnaiyan, Arul;Rasky, Andrew J.;Morris, Susan;Yagi, Kazuma;Bermick, Jennifer R.;Lukacs, Nicholas W.
- 通讯作者:Lukacs, Nicholas W.
Effect of prenatal dog exposure on eczema development in early and late childhood.
- DOI:10.1016/j.jaip.2022.09.007
- 发表时间:2022-12
- 期刊:
- 影响因子:9.4
- 作者:Eapen, Amy A.;Sitarik, Alexandra R.;Cheema, Gagandeep;Kim, Haejin;Ownby, Dennis;Johnson, Christine C.;Zoratti, Edward
- 通讯作者:Zoratti, Edward
Dogs, cats, and asthma: Will we ever really know the true risks and benefits?
狗、猫和哮喘:我们真的能知道真正的风险和好处吗?
- DOI:10.1016/j.jaci.2016.08.021
- 发表时间:2016
- 期刊:
- 影响因子:0
- 作者:Ownby,DennisR;Johnson,ChristineCole
- 通讯作者:Johnson,ChristineCole
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{{ truncateString('Christine C Johnson', 18)}}的其他基金
Human Epidemiology and Response to SARS-CoV-2 (HEROS)
人类流行病学和对 SARS-CoV-2 的反应 (HEROS)
- 批准号:
10167014 - 财政年份:2020
- 资助金额:
$ 299.46万 - 项目类别:
Pets and the Infant's Microbiome Exposures: Impac on Childhood Allergic Asthma
宠物和婴儿的微生物组暴露:对儿童过敏性哮喘的影响
- 批准号:
9088338 - 财政年份:2016
- 资助金额:
$ 299.46万 - 项目类别:
Personalizing Care for Obese Patients in an Urban Health System
城市卫生系统中肥胖患者的个性化护理
- 批准号:
9340014 - 财政年份:2013
- 资助金额:
$ 299.46万 - 项目类别:
Personalizing Care for Obese Patients in an Urban Health System
城市卫生系统中肥胖患者的个性化护理
- 批准号:
8737239 - 财政年份:2013
- 资助金额:
$ 299.46万 - 项目类别:
Personalizing Care for Obese Patients in an Urban Health System
城市卫生系统中肥胖患者的个性化护理
- 批准号:
8600372 - 财政年份:2013
- 资助金额:
$ 299.46万 - 项目类别:
Pets and the Infant Microbiome: Effect on Immune Maturation & Atopic Asthma
宠物和婴儿微生物组:对免疫成熟的影响
- 批准号:
8339505 - 财政年份:2012
- 资助金额:
$ 299.46万 - 项目类别:
Pets and the Infant Microbiome: Effect on Immune Maturation & Atopic Asthma
宠物和婴儿微生物组:对免疫成熟的影响
- 批准号:
9088296 - 财政年份:2012
- 资助金额:
$ 299.46万 - 项目类别:
Pets and the Infant Microbiome: Effect on Immune Maturation & Atopic Asthma
宠物和婴儿微生物组:对免疫成熟的影响
- 批准号:
8881054 - 财政年份:2012
- 资助金额:
$ 299.46万 - 项目类别:
Pets and the Infant Microbiome: Effect on Immune Maturation & Atopic Asthma
宠物和婴儿微生物组:对免疫成熟的影响
- 批准号:
8676640 - 财政年份:2012
- 资助金额:
$ 299.46万 - 项目类别:
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