Project 4 Alteration of Mouse Maternal Gut Microbiota Alters Metabolic Profiles and Immune Phenotype in Offspring
Project 4 Alteration of Mouse Maternal Gut Microbiota Alters Metabolic Profiles and Immune Phenotype in Offspring
批准号:
10480058
负责人:
Nicholas W Lukacs
金额:
$115.23万
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
项目状态:
未结题
起止时间:
2012-07-06 至 2025-08-31
关键词:
10 year oldAddressAffectAllergensAllergicAllergic DiseaseAnimal ModelAnimalsAsthmaBacteriaBlood CirculationBone MarrowBreast FeedingBreedingCanis familiarisCell physiologyCellsChildChildhoodClinical ResearchDataDendritic CellsDevelopmentDiseaseDustEnvironmentExtrinsic asthmaFemaleFosteringHealthHomeHomeostasisHouse DustHumanHuman MilkHypersensitivityImmuneImmune responseInfantInstitutesIntestinesKnowledgeLactobacillusLeadLifeLipidsLung immune responseMetabolicMothersMusNeonatalOmega-3 Fatty AcidsPartner in relationshipPathogenicityPathologicPathologyPhenotypePopulationPostpartum PeriodPredispositionPregnancyPulmonary InflammationResistanceRespiratory Syncytial Virus InfectionsRespiratory syncytial virusRiskShapesStimulusSupplementationSystemTestingWeaningallergic responseattenuationbaseeffective interventionepidemiology studyexperimental studygut microbiotahigh riskin uteroindividualized preventioninsightlong-term sequelaematernal microbiomematernal microbiotametabolic profilemetabolomemicrobialmicrobiomemicrobiotamouse modelneonatal infectionneonatal miceneonateoffspringoral supplementationpet animalpreclinical studypupresponse
中文摘要
在我们最初的P01中,我们发现口服了有狗的家中的灰尘的老鼠对
英文摘要
In our initial P01, we found that mice orally supplemented with dust from homes with dogs were resistant to
induction of allergic lung inflammation compared to mice supplemented with dust from homes without pets.
Examination of ceca from mice supplemented dog-home dust identified a keystone species, Lactobacillus
johnsonii. Oral supplementation of mice with viable but not killed L. johnsonii reduced susceptibility to induction
of both allergic and respiratory syncytial virus (RSV) induced lung inflammation. These reductions in lung
inflammation appear to be related to alterations in the functional activity of bone marrow-derived dendritic cells
(DC). Preliminary data suggests that microbial metabolites in the circulation of supplemented animals differ
from those of un-supplemented animals. Limited data suggests that the differences in circulating metabolites
are responsible for the alterations in DC function. Our rationale for including studies of RSV are epidemiologic
studies showing that RSV infections in human infants increase the risk of subsequent asthma. Our mouse
models mirror this relationship since neonatal infection with RSV leads to greater pathology when the mice are
sensitized to allergen 4 weeks later. Interestingly our preliminary studies have shown that supplementation of
female mice with L. johnsonii prior to mating reduces responses to allergen and RSV challenges in offspring to
a level similar to that observed in directly supplemented mice. Among the questions raised by this observation
was whether the effects of maternal supplementation on offspring occurred during in utero development or
post-partum from components of breast milk. This question led to cross-fostering experiments. In these
experiments offspring of supplemented or un-supplemented mice were nursed by either supplemented or un-
supplemented mothers revealing that breast feeding can partially protect pups of un-supplemented mothers
from RSV. Based on our findings we propose studies in this Project based on the hypothesis that the maternal
microbiota shapes the developing neonatal immune homeostatic mechanisms through alteration of the
offspring gut microbiota and related microbial metabolites which lead to differences in immune responsiveness
and the risk of pathogenic allergic responses. Our studies will continue to examine the mechanisms though
which microbial changes affect pathologic responses to allergens and RSV. These studies will include further
studies to differentiate in utero effects and breast milk effects on offspring. Finally, we will examine the effects
of supplementation with consortia of bacteria selected in Project 3 on the response of offspring to allergen and
RSV challenges. These studies will provide greater insight into the findings from the human studies in Projects
1 & 2, especially questions concerning when effective interventions might be most safely instituted.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Viral and allergen-driven immunity in chronic lung disease
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批准号:10347313
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项目类别:
-
资助金额:$68.49万
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财政年份:2020
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负责人:Nicholas W Lukacs
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依托单位:
Viral and allergen-driven immunity in chronic lung disease
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批准号:10551728
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项目类别:
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资助金额:$68.49万
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财政年份:2020
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负责人:Nicholas W Lukacs
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依托单位:
Viral and allergen-driven immunity in chronic lung disease
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批准号:9886480
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项目类别:
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资助金额:$68.49万
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财政年份:2020
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负责人:Nicholas W Lukacs
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依托单位:
Autophagy regulation of RSV-induced pulmonary disease
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批准号:8515518
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项目类别:
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资助金额:$36.46万
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财政年份:2012
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负责人:Nicholas W Lukacs
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依托单位:
Autophagy regulation of RSV-induced pulmonary disease
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批准号:8340769
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项目类别:
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资助金额:$38.31万
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财政年份:2012
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负责人:Nicholas W Lukacs
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依托单位:
Autophagy regulation of RSV-induced pulmonary disease
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批准号:8687732
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项目类别:
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资助金额:$37.51万
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财政年份:2012
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负责人:Nicholas W Lukacs
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依托单位:
Autophagy regulation of RSV-induced pulmonary disease
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批准号:8871569
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项目类别:
-
资助金额:$38.29万
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财政年份:2012
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负责人:Nicholas W Lukacs
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依托单位:
TLR and Notch Ligand in RSV-induced Disease
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批准号:7878285
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项目类别:
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资助金额:$1.79万
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财政年份:2009
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负责人:Nicholas W Lukacs
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依托单位:
The Role of C-C Chemokines in Eosinophil Airway Inflammation
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批准号:7846595
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项目类别:
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资助金额:$6.64万
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财政年份:2009
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负责人:Nicholas W Lukacs
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依托单位:
TLR and Notch Ligand in RSV-induced Disease
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批准号:8206794
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项目类别:
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资助金额:$36.48万
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财政年份:2008
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负责人:Nicholas W Lukacs
-
依托单位:
TLR and Notch Ligand in RSV-induced Disease
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批准号:7555072
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项目类别:
-
资助金额:$37.22万
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财政年份:2008
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负责人:Nicholas W Lukacs
-
依托单位:
TLR and Notch Ligand in RSV-induced Disease
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批准号:7367334
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项目类别:
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资助金额:$37.22万
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财政年份:2008
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负责人:Nicholas W Lukacs
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依托单位:
TLR and Notch Ligand in RSV-induced Disease
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批准号:7742163
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项目类别:
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资助金额:$36.85万
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财政年份:2008
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负责人:Nicholas W Lukacs
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依托单位:
TLR and Notch Ligand in RSV-induced Disease
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批准号:7999240
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项目类别:
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资助金额:$36.48万
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财政年份:2008
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负责人:Nicholas W Lukacs
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依托单位:
Cockroach Allergen-Induced Airway Inflammation
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批准号:7350228
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项目类别:
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资助金额:$38.28万
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财政年份:2007
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负责人:Nicholas W Lukacs
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依托单位:
Cockroach Allergen-Induced Airway Inflammation
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批准号:7312446
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项目类别:
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资助金额:$34.88万
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财政年份:2006
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负责人:Nicholas W Lukacs
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依托单位:
Cockroach Allergen-Induced Airway Inflammation
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批准号:6969306
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项目类别:
-
资助金额:$33.86万
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财政年份:2004
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负责人:Nicholas W Lukacs
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依托单位:
COCKROACH ALLERGEN INDUCED AIRWAY INFLAMMATION
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批准号:6302198
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项目类别:
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资助金额:$22.43万
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财政年份:2000
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负责人:Nicholas W Lukacs
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依托单位:
SCF in Allergic Airway Inflammation
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批准号:6895577
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项目类别:
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资助金额:$29.52万
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财政年份:1999
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负责人:Nicholas W Lukacs
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依托单位:
SCF in Allergic Airway Inflammation
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批准号:7058767
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项目类别:
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资助金额:$28.65万
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财政年份:1999
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负责人:Nicholas W Lukacs
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依托单位:
海外基金