Biological signatures of blueberry derived microbial metabolites
Biological signatures of blueberry derived microbial metabolites
批准号:
10229449
负责人:
Anandh Babu Pon Velayutham
金额:
$38.13万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-09-21 至 2024-05-31
关键词:
AnthocyaninsAttenuatedBacteriaBerryBifidobacteriumBiologicalBiological AvailabilityBlood VesselsBlueberriesCardiovascular DiseasesDataDependenceDevelopmentDiabetic mouseDietary ComponentDietary intakeDoseDyslipidemiasEndothelial CellsEndotheliumEpidemicFamilyFlavonoidsFruitFunctional disorderGerm-FreeGlycocalyxGlycosaminoglycansGoalsGrowthHealthHeparan Sulfate ProteoglycanHigh Fat DietHumanHyperglycemiaHypertensionIi-KeyIndividualInflammationInflammatoryIntakeLinkMediatingMedical Care CostsMetabolic DiseasesMetabolic syndromeMetagenomicsMethodsMicrobeModelingMolecularMolecular TargetMusNitric OxideNutritionalOrganismPalmitatesPathway interactionsPermeabilityPhysiologicalPlasmaPlayPopulationProductionPublic HealthResearchRoleSerumSideStimulusSupplementationSurfaceTechniquesTimeTissuesUrsidae FamilyVascular DiseasesVascular EndotheliumVasodilationWorkatherogenesisbaseblood pressure reductioncardiovascular risk factorcostcost effectivecytokinedb/db mousediabeticdiabetic patientdietaryendothelial dysfunctiongut bacteriagut microbiomegut microbiotaheparin proteoglycanimprovedinnovationmenmetabolomicsmicrobialmicrobiotamortalitymultiple omicsnovelnovel strategiespreservationpressurepreventproteoglycan core proteinrestorationtraditional therapytranscriptome sequencingvascular inflammation
中文摘要
项目摘要/摘要
英文摘要
PROJECT SUMMARY/ ABSTRACT
The goal of this study is to identify the molecular mechanisms by which blueberry-derived microbial
metabolites improve endothelial dysfunction during metabolic syndrome (MetS). We will employ multiomics
approaches to determine the vascular effects of blueberry metabolites. MetS is an important risk factor for
cardiovascular mortality and endothelial dysfunction plays a major role in the development of vascular
complications. Hyperglycemia, dyslipidemia, and pro-inflammatory cytokines contribute to endothelial
dysfunction in MetS. The vascular endothelium is covered with a glycocalyx which is comprised of proteoglycans
[core proteins with glycosaminoglycans (GAG)]. Intact glycocalyx of healthy vasculature acts as a protective
barrier and prevents endothelial dysfunction. Glycocalyx, importantly heparan sulfate proteoglycan (HSPG), is
severely compromised in MetS. Hence, preservation and restoration of HSPG to improve endothelial dysfunction
is a novel strategy to ameliorate vascular complications in MetS. Human studies support the vascular effects of
blueberry anthocyanins. Anthocyanins are extensively metabolized by the gut microbiota in humans, suggesting
their vascular benefits might be mediated by their microbial metabolites. Gut microbiota metabolize anthocyanins
and anthocyanins support the growth of microbes indicating a two-way relationship between them. Our
preliminary data show that :(i) blueberry supplementation improves vascular inflammation and dysfunction, and
increases the beneficial bacteria in diabetic mice; (ii) key blueberry metabolites attenuate palmitate-induced
endothelial inflammation and vascular dysfunction, and increase GAG production in endothelial cells (ECs)
isolated from diabetic patients. However, studies are lacking that identify (i) the microbial metabolites of
blueberries (Aim 1), (ii) the mechanisms by which blueberry-derived microbial metabolites improve endothelial
dysfunction in MetS (Aim 2), and (iii) the most active metabolites responsible for the vascular effects of
blueberries (Aim 3). Based on our preliminary studies, we hypothesize that blueberry attenuates endothelial
dysfunction in MetS by improving HSPG and/or acting on multiple targets which is mediated through the microbial
metabolites of blueberries. (1) Aim 1A: Determine the optimal dose of blueberry required to improve vascular
inflammation and dysfunction in mice with MetS using two established models [diabetic db/db mice and high fat
diet (HFD)-fed mice]. Aim 1B: Identify blueberry-derived `microbial metabolites'. (2) Aim 2: Determine the
mechanisms by which blueberry-derived microbial metabolites improve endothelial dysfunction in MetS. (3) Aim
3A: Determine the impact of circulating metabolites on endothelial dysfunction. Aim 3B. Identify the most active
microbial metabolite(s). We will use physiologically relevant models and state of the art techniques to evaluate
the mechanistic roles of microbial metabolites of blueberries at the cellular level, tissue level and organism level.
Our study will provide strong scientific rationale for recommending dietary intake of blueberries to improve
vascular health in the US population and worldwide.
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DOI:
10.1080/10408398.2023.2251616
发表时间:
2023-08
期刊:
Critical reviews in food science and nutrition
影响因子:
10.2
作者:
[Adhini Kuppuswamy Satheesh Babu;Harini Srinivasan;Pon Velayutham Anandh Babu]
通讯作者:
Adhini Kuppuswamy Satheesh Babu;Harini Srinivasan;Pon Velayutham Anandh Babu
DOI:
10.1002/mnfr.202300096
发表时间:
2023-07
期刊:
Molecular nutrition & food research
影响因子:
5.2
作者:
[C. M. Della Lucia;L. Oliveira;K. A. Dias;S. Pereira;Aline Rosignoli da Conceição;Pon Velayutham Anandh Babu]
通讯作者:
C. M. Della Lucia;L. Oliveira;K. A. Dias;S. Pereira;Aline Rosignoli da Conceição;Pon Velayutham Anandh Babu
DOI:
10.1016/j.ebiom.2023.104641
发表时间:
2023-07
期刊:
EBIOMEDICINE
影响因子:
11.1
作者:
[Mokhtari, Pari, Jambal, Puujee, Metos, Julie M., Shankar, Kartik, Babu, Pon Velayutham Anandh]
通讯作者:
Babu, Pon Velayutham Anandh
DOI:
10.1007/978-1-0716-1398-6_37
发表时间:
2022-01-01
期刊:
Methods in molecular biology (Clifton, N.J.)
影响因子:
--
作者:
[Cutler, Brett Ronald, Chua, Jie Shi, Anandh Babu, Pon Velayutham]
通讯作者:
Anandh Babu, Pon Velayutham
Dose and Time Dependent Effect of Dietary Blueberries on Diabetic Vasculature is Associated with Gut Microbes.
膳食蓝莓对糖尿病脉管系统的剂量和时间依赖性影响与肠道微生物有关。
DOI:
--
发表时间:
2022
期刊:
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子:
--
作者:
[SatheeshBabu,AdhiniKuppuswamy, Petersen,Chrissa, Wankhade,Umesh, Paz,Henry, Benedict,Kai, Nguyen,Miley, Putich,Madison, Saldivar-Gonzalez,Miguel, Larsen,Sydney, PonVelayutham,AnandhBabu]
通讯作者:
PonVelayutham,AnandhBabu
共 9 条
Biological signatures of blueberry derived microbial metabolites
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批准号:9789191
-
项目类别:
-
资助金额:$38.23万
-
财政年份:2018
-
负责人:Anandh Babu Pon Velayutham
-
依托单位:
海外基金