Diet and metabolic factors in the pathogenesis of microscopic colitis
饮食和代谢因素在微小结肠炎发病机制中的作用
基本信息
- 批准号:10556332
- 负责人:
- 金额:$ 19.62万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-02-01 至 2026-11-30
- 项目状态:未结题
- 来源:
- 关键词:AdherenceAffectAgeAlgorithmsAnti-Inflammatory AgentsAreaAwardBiologicalBlood specimenButyratesCell membraneCharacteristicsClinicalColitisColonic inflammationColorectal CancerConsumptionCuesDataDevelopmentDiagnosticDietDiet therapyDietary FactorsDietary FiberDietary PracticesDiseaseDisease OutcomeElderlyEnvironmentEnvironmental Risk FactorEpidemiologyFDA approvedFacultyFemaleFishesFollow-Up StudiesFoodFruitFunctional disorderFutureGastroenterologistGeneral HospitalsGeneticGoalsHealth ProfessionalImmune ToleranceImmune responseImmunityImpairmentIncidenceIndividualInflammatoryInflammatory Bowel DiseasesIntakeIntestinesLarge IntestineLinkLongitudinal cohortLymphocyteMaintenanceMassachusettsMeasuresMeatMediatingMediterranean DietMentorsMentorshipMetabolicMetabolic PathwayMicroscopic ColitisModelingNested Case-Control StudyNurses&apos Health StudyOutcomePathogenesisPathway interactionsPatient-Focused OutcomesPatientsPatternPhysiciansPlasmaPlayPrediction of Response to TherapyPrevention strategyPreventive treatmentProcessProcessed MeatsProductionProspective cohortPublic Health SchoolsQuality of lifeRecommendationRelapseResearchResearch PersonnelRiskRoleShapesSphingolipidsT-LymphocyteTestingTrainingTreatment outcomeTryptophanTryptophan Metabolism PathwayUnited States National Institutes of HealthVegetablesVolatile Fatty AcidsWorkcareercareer developmentchronic inflammatory diseasecohortcytokinedietaryfruits and vegetablesgastrointestinal epitheliumgut inflammationgut microbiomeimmune activationinflammatory markerinsightinterestintraepitheliallymphocyte traffickingmalemetabolic abnormality assessmentmetabolic profilemetabolomicsmicrobiomemicrobiome compositionnovelnutritional epidemiologypopulation basedprospectivesextherapeutic targettreatment responsetreatment strategy
项目摘要
PROJECT SUMMARY/ABSTRACT
Microscopic colitis (MC) is a debilitating T-cell-mediated inflammatory disease of the large intestine with an
incidence that now rivals that of inflammatory bowel disease (IBD), but has no FDA-approved therapies.
Emerging evidence supports that MC occurs due to an inappropriate immune response to environmentally-
induced disturbances in the luminal microenvironment. Diet is a critical regulator of the luminal microenvironment
through alteration in gut epithelial integrity, microbiome composition and function, and immune cell activation.
Yet, its role in the pathogenesis of MC remains unknown. Two dietary patterns, the Empiric Dietary Inflammatory
Pattern (EDIP) and the Mediterranean diet, are of particular interest in MC pathogenesis due to their associations
with changes in downstream metabolites, including short chain fatty acids, sphingolipids, and tryptophan
metabolites, that have a plausible mechanistic basis in MC and a known role in the pathogenesis of other models
of colitis. Furthermore, these dietary patterns and downstream metabolic pathways are associated with 1)
systemic inflammatory markers known to be elevated in MC, and 2) incidence, disease activity, and treatment
response of other IBD. Accordingly, our overarching hypothesis is that specific metabolic pathways,
influenced by diet, impact risk of incident disease and treatment outcomes in MC. To test this hypothesis,
we will first examine the associations between derived dietary patterns, EDIP and modified Mediterranean diet
(Aim 1a), and their individual components (Aim 1b) and risk of MC within three population-based cohorts, the
Nurses’ Health Studies and Health Professionals Follow-up Study. Second, within these cohorts we will evaluate
the association between plasma metabolites and risk of MC (Aim 2a), and determine if metabolites mediate the
associations between diet and MC (Aim 2b). Third, we will evaluate metabolites that predict therapeutic response
in a prospective cohort of individuals with incident MC at Massachusetts General Hospital (MGH). We anticipate
this work will provide valuable insight into the pathogenesis of MC, offering the basis for novel dietary therapies
for MC in the future. Further, it will promote the career development of a junior faculty gastroenterologist at MGH
with the long-term career goal of becoming an independent physician-investigator, focused on defining the
etiopathogenesis of disease to inform preventive strategies and treatment algorithms that enhance patient
outcomes. To achieve this goal, this proposal builds on the candidate’s background in epidemiology to provide
focused training in nutritional epidemiology, analysis of metabolomic data to understand implicated biological
pathways, and prospective cohort development. The candidate will thrive with the support of 1) a renowned
mentorship team with expertise in MC, nutritional epidemiology, and metabolomics, 2) experiential and formal
didactic training, and 3) the outstanding scientific environment of the MGH Clinical and Translational
Epidemiology Unit, Harvard School of Public Health, and Broad Institute. By the completion of this award, the
candidate will demonstrate the scientific independence and preliminary data for a successful R01 application.
项目总结/文摘
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)
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Kristin E. Burke其他文献
Sa1790 NEIGHBORHOOD GREENNESS AND RISK OF INFLAMMATORY BOWEL DISEASE
- DOI:
10.1016/s0016-5085(23)02004-8 - 发表时间:
2023-05-01 - 期刊:
- 影响因子:
- 作者:
Michaela Tracy;Emily W. Lopes;Kristin E. Burke;Ashwin Ananthakrishnan;James Richter;Andrew T. Chan;Jaime E. Hart;Hamed Khalili - 通讯作者:
Hamed Khalili
Comparative Effectiveness of Upadacitinib and Tofacitinib in Inducing Remission in Ulcerative Colitis: Real-World Data
乌帕替尼和托法替尼在诱导溃疡性结肠炎缓解方面的比较有效性:真实世界数据
- DOI:
10.1016/j.cgh.2023.03.040 - 发表时间:
2023-08-01 - 期刊:
- 影响因子:12.000
- 作者:
Leo Boneschansker;Ashwin N. Ananthakrishnan;Kristin E. Burke;Bharati D. Kochar;Emily W. Lopes;Hamed Khalili;Francis Colizzo - 通讯作者:
Francis Colizzo
Sa1555: PREDIAGNOSTIC LEVELS OF CIRCULATING METABOLITES ARE ASSOCIATED WITH THE RISK OF INFLAMMATORY BOWEL DISEASE
- DOI:
10.1016/s0016-5085(22)60982-x - 发表时间:
2022-05-01 - 期刊:
- 影响因子:
- 作者:
Xinwei Hua;Ryan C. Ungaro;Francesca Petralia;Emily W. Lopes;Kristin E. Burke;Ashwin Ananthakrishnan;James Richter;Amit D. Joshi;Renee M. Laird;Chad K. Porter;Mark S. Riddle;Clary B. Clish;Lauren Petrick;Jean Frederic Colombel;Andrew Chan;Hamed Khalili - 通讯作者:
Hamed Khalili
Sa2031 SINGLE-CELL TRANSCRIPTOMIC CHARACTERIZATION OF MICROSCOPIC COLITIS
- DOI:
10.1016/s0016-5085(24)01867-5 - 发表时间:
2024-05-18 - 期刊:
- 影响因子:
- 作者:
Stefan Halvorsen;Molly Thomas;Mari Mino-Kenudson;Kristin E. Burke;David Morgan;Kaia C. Miller;Jessica McGoldrick;Joseph C. Yarze;Kyle Staller;Daniel Chung;Alexandra-Chloé Villani;Slim Sassi;Hamed Khalili - 通讯作者:
Hamed Khalili
389 ULTRA-PROCESSED FOODS AND RISK OF CROHN'S DISEASE AND ULCERATIVE COLITIS: A PROSPECTIVE COHORT STUDY
- DOI:
10.1016/s0016-5085(21)00936-7 - 发表时间:
2021-05-01 - 期刊:
- 影响因子:
- 作者:
Chun-Han Lo;Neha Khandpur;Sinara L. Rossato;Paul Lochhead;Emily W. Lopes;Kristin E. Burke;James Richter;Mingyang Song;Andres Ardisson Korat;Qi Sun;Teresa Fung;Hamed Khalili;Andrew Chan;Ashwin Ananthakrishnan - 通讯作者:
Ashwin Ananthakrishnan
Kristin E. Burke的其他文献
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{{ truncateString('Kristin E. Burke', 18)}}的其他基金
Diet and metabolic factors in the pathogenesis of microscopic colitis
饮食和代谢因素在微小结肠炎发病机制中的作用
- 批准号:
10351330 - 财政年份:2022
- 资助金额:
$ 19.62万 - 项目类别:
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