Metabolic correlates of disease activity and disability progression in pediatric MS
儿科多发性硬化症疾病活动性和残疾进展的代谢相关性
基本信息
- 批准号:10380775
- 负责人:
- 金额:$ 40.18万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-04-01 至 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:16S ribosomal RNA sequencingAdultAffectAgeAgingAnimal ModelAnti-Inflammatory AgentsBiologicalBiological ProcessBiological Response Modifier TherapyBloodBody mass indexChildChildhoodClinicalComplexCox Proportional Hazards ModelsDataDietDietary FiberDietary intakeDigit structureDiseaseDisease MarkerDisease OutcomeDisease ProgressionDisease modelDocosahexaenoic AcidsDyslipidemiasEndocannabinoidsEnergy MetabolismEnvironmental ExposureEnvironmental Risk FactorEthnic OriginEtiologyExperimental Autoimmune EncephalomyelitisFatty AcidsFatty acid glycerol estersFecesFermentationFoodFrequenciesFunctional disorderFutureGeneticGenetic RiskGoalsHigh Fat DietImmune responseImpaired cognitionIn VitroIndividualInflammationInflammation MediatorsInflammatoryInjuryIntakeInterventionIntervention StudiesIntervention TrialInvestigationIsotope LabelingLeast-Squares AnalysisLesionLinkLipidsLipoxygenaseLiquid ChromatographyLiteratureMagnetic Resonance ImagingMass FragmentographyMeasuresMediationMediator of activation proteinMetabolicMetabolic PathwayModalityModelingMultiple SclerosisMultivariate AnalysisNeurologicObesityPathogenesisPathway AnalysisPathway interactionsPeripheralPlasmaPositioning AttributePropertyPropionatesRaceRegression AnalysisRegulationRelapseReportingResearchResourcesRiskRisk FactorsSerumSignaling MoleculeSocietiesSupplementationTestingTryptophanTryptophan Metabolism PathwayUnited States National Institutes of HealthVegetablesVitamin DVolatile Fatty Acidsadipokinesage groupbiobankclinical translationcognitive changecognitive disabilitycomorbiditydata reductiondesigndisabilityeffective therapyforestgenetic makeupgenetic variantgut metagenomegut microbiomehigh riskimmunoregulationinflammatory markerinterestlipid mediatorlipidomicsmachine learning algorithmmetabolomemetabolomicsmultiple sclerosis patientpediatric multiple sclerosispediatric patientsphysically handicappedrelapse risksaturated fatsexsocioeconomicsstool sampletandem mass spectrometrytooltreatment strategy
项目摘要
PROJECT SUMMARY
The biological processes contributing to relapses and disability progression in multiple sclerosis (MS) remain
largely unknown. During the past decade, our pediatric MS Network has investigated risk factors in children. We
have discovered that higher saturated fat and lower vegetable dietary intake may independently increase the
risk of relapse in those with the disease. Our preliminary findings, consistent with the association of high fat diet
with higher risk of MS relapse, suggest that higher plasma levels of three acyl-ethanolamides
(endocannabinoids) and docosahexaenoic acid (DHA) may be associated with higher relapse risk in children.
Lipids mediators such as oxylipins and endocannabinoids have immunomodulatory properties and some are
neuroprotective. Their plasma levels are influenced among others by dietary intake, obesity status and genetic
profile. Furthermore, our findings that the tryptophan pathway is associated with the risk of relapse and disease
progression links plausibly to expected changes in short chain fatty acids that we plan to investigate.
Although MS is less common in children, studies in this age group have several important advantages including
less irrelevant exposures and comorbidities that result from aging. With previous NIH and National MS Society
support, we have established a highly collaborative national research group and a unique resource that will be
leveraged in this proposal to test new hypotheses. We propose state-of-the-art untargeted and targeted
metabolomics and lipidomics analyses to determine the association of various plasma and stool lipids and their
mediators with the risk of subsequent relapse, new MRI lesions, and neurologic and cognitive impairment. Each
individual has extensive demographic, clinical, MRI, genetic, food frequency and environmental exposure data.
Analyses will be adjusted for possible confounders such as age, sex, race, ethnicity, socioeconomic profile, use
of disease-modifying therapy, body mass index and serum 25(OH) vitamin D. We will also model the contribution
of various metabolites in the context of adipokines, food frequency, gut microbiome profile and genetic variants
that modulate plasma lipid and mediator levels. This sophisticated modelling including pathway analyses will
establish which of the variables are independent predictors.
Our group of collaborators with expertise in metabolomics, lipidomics, genetics, and environmental risk factors
is in a unique position to significantly advance the understanding of MS pathogenesis. The findings in the
proposed study will unravel biological links between diet, gut microbiome, obesity and MS course. Although
longitudinal association studies do not confirm causality, they are critical to identify putative biological pathways
that may contribute to disease activity and progression. Intervention studies cannot be designed if associations
are unknown. Our proposed investigation has strong potential for clinical translation as we will identify biological
targets that can then be tested for causality in proof-of-concept MS trials with interventions such as
supplementation with live biotherapeutic products influencing metabolic pathways of interest.
项目摘要
导致多发性硬化症(MS)复发和残疾进展的生物学过程仍然存在
大部分未知。在过去的十年中,我们的儿科MS网络调查了儿童的风险因素。我们
他们发现,高饱和脂肪和低蔬菜饮食摄入量可能独立地增加
复发的风险。我们的初步研究结果,与高脂肪饮食的关联一致
MS复发风险较高,表明三种酰基乙醇酰胺的血浆水平较高,
(内源性大麻素)和二十二碳六烯酸(DHA)可能与儿童复发风险较高有关。
脂质介质如氧脂素和内源性大麻素具有免疫调节特性,并且一些具有免疫调节特性。
神经保护他们的血浆水平受饮食摄入、肥胖状况和遗传因素等的影响。
profile.此外,我们发现色氨酸途径与复发和疾病的风险有关,
进展与我们计划研究的短链脂肪酸的预期变化有着必然的联系。
虽然MS在儿童中不太常见,但在该年龄组中进行的研究具有几个重要的优势,包括
减少不相关的暴露和老化导致的合并症。与以前的NIH和国家MS协会
在支持下,我们建立了一个高度合作的国家研究小组和一个独特的资源,
在这个提案中利用来测试新的假设。我们建议采用最先进的非目标性和目标性
代谢组学和脂质组学分析,以确定各种血浆和粪便脂质及其
具有随后复发、新MRI病变以及神经和认知障碍风险的介质。每个
个体具有广泛的人口统计学、临床、MRI、遗传、食物频率和环境暴露数据。
分析将根据可能的混杂因素进行调整,如年龄、性别、人种、种族、社会经济学特征、使用
疾病改善治疗,体重指数和血清25(OH)维生素D。我们还将模拟贡献
在脂肪因子、食物频率、肠道微生物组谱和遗传变异的背景下,
调节血浆脂质和介质水平。包括路径分析在内的复杂建模将
确定哪些变量是独立预测变量。
我们的合作者团队在代谢组学,脂质组学,遗传学和环境风险因素方面具有专业知识
是在一个独特的位置,以显着推进MS发病机制的理解。中的调查结果
拟议的研究将揭示饮食,肠道微生物组,肥胖和MS课程之间的生物学联系。虽然
纵向关联研究不能证实因果关系,但对于确定假定的生物学途径至关重要
可能导致疾病活动和进展。干预研究不能设计,如果协会
是未知的。我们提出的研究具有很强的临床转化潜力,因为我们将确定生物学
然后可以在概念验证MS试验中测试因果关系的目标,
补充影响感兴趣的代谢途径的活生物活性物质产品。
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 }}
EMMANUELLE LAURENCE WAUBANT其他文献
EMMANUELLE LAURENCE WAUBANT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('EMMANUELLE LAURENCE WAUBANT', 18)}}的其他基金
Metabolic correlates of disease activity and disability progression in pediatric MS
儿科多发性硬化症疾病活动性和残疾进展的代谢相关性
- 批准号:
10210165 - 财政年份:2021
- 资助金额:
$ 40.18万 - 项目类别:
Metabolic correlates of disease activity and disability progression in pediatric MS
儿科多发性硬化症疾病活动性和残疾进展的代谢相关性
- 批准号:
10593945 - 财政年份:2021
- 资助金额:
$ 40.18万 - 项目类别:
Environmental and genetic risk factors for pediatric MS
儿童多发性硬化症的环境和遗传危险因素
- 批准号:
8259849 - 财政年份:2010
- 资助金额:
$ 40.18万 - 项目类别:
Environmental and genetic risk factors for pediatric MS
儿童多发性硬化症的环境和遗传危险因素
- 批准号:
8460902 - 财政年份:2010
- 资助金额:
$ 40.18万 - 项目类别:
Environmental and genetic risk factors for pediatric MS
儿童多发性硬化症的环境和遗传危险因素
- 批准号:
8122240 - 财政年份:2010
- 资助金额:
$ 40.18万 - 项目类别:
Environmental and genetic risk factors for pediatric MS
儿童多发性硬化症的环境和遗传危险因素
- 批准号:
7950045 - 财政年份:2010
- 资助金额:
$ 40.18万 - 项目类别:
相似海外基金
Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
- 批准号:
MR/Z503605/1 - 财政年份:2024
- 资助金额:
$ 40.18万 - 项目类别:
Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
- 批准号:
2336167 - 财政年份:2024
- 资助金额:
$ 40.18万 - 项目类别:
Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
- 批准号:
2402691 - 财政年份:2024
- 资助金额:
$ 40.18万 - 项目类别:
Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
- 批准号:
24K12150 - 财政年份:2024
- 资助金额:
$ 40.18万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
- 批准号:
2341428 - 财政年份:2024
- 资助金额:
$ 40.18万 - 项目类别:
Standard Grant
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
- 批准号:
DE240100561 - 财政年份:2024
- 资助金额:
$ 40.18万 - 项目类别:
Discovery Early Career Researcher Award
Laboratory testing and development of a new adult ankle splint
新型成人踝关节夹板的实验室测试和开发
- 批准号:
10065645 - 财政年份:2023
- 资助金额:
$ 40.18万 - 项目类别:
Collaborative R&D
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
- 批准号:
23K09542 - 财政年份:2023
- 资助金额:
$ 40.18万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
- 批准号:
23K07552 - 财政年份:2023
- 资助金额:
$ 40.18万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
- 批准号:
23K07559 - 财政年份:2023
- 资助金额:
$ 40.18万 - 项目类别:
Grant-in-Aid for Scientific Research (C)