Evaluation of the gut-kidney axis in kidney stone disease
肾结石疾病中肠-肾轴的评估
基本信息
- 批准号:9802990
- 负责人:
- 金额:$ 72.65万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-07-01 至 2023-04-30
- 项目状态:已结题
- 来源:
- 关键词:4 year oldAdolescentAdultAffectAgeAge-YearsAntibioticsBacteriaButyratesCalciumCardiovascular DiseasesCephalosporinsChemistryChildChronic Kidney FailureClinical DataCohort StudiesCommunitiesComplexDataData AnalyticsData LinkagesDatabasesDiabetes MellitusDietDiseaseDoseEnvironmental ExposureEvaluationEventExcretory functionExposure toFecesFluoroquinolonesFractureFutureGoalsGut MucosaHealthHourHumanHypertensionIncidenceIndividualIntakeIntestinal AbsorptionIntestinesKidneyKidney CalculiLeadLifeLinkMacronutrients NutritionMeasuresMediatingMediationMedicalMetabolicMetabolic PathwayMetabolismMetagenomicsMineralsModelingMorbidity - disease rateNephrolithiasisNested Case-Control StudyNitrofurantoinNutritionalOralOrganismOxalatesOxalobacterOxalobacter formigenesPainParticipantPatientsPenicillinsPharmacoepidemiologyPharmacologic SubstancePharmacy facilityPopulationPrevalencePreventionReportingResearchResearch DesignRiskRisk FactorsRoleShotgunsSubgroupTestingTimeUnited StatesUrinary tractUrineVolatile Fatty AcidsZinccostdysbiosisgut microbiomehigh dimensionalityinsightmetabolomemetabolomicsmicrobial communitymicrobiomemicrobiome alterationmultidimensional datanew therapeutic targetnovelpreventtherapeutic targeturinaryyoung woman
项目摘要
PROJECT SUMMARY
Kidney stone disease is highly prevalent, increasingly common, and associated with considerable morbidity.
However, no new treatments to prevent kidney stones have been introduced in the last 30 years. Understanding
how dysbiosis of the gut microbiome contributes to nephrolithiasis could lead to novel new treatments for kidney
stone prevention. However, most prior studies of the gut microbiome in this population focused on Oxalobacter
formigenes without considering the role of the entire gut microbiome in the gut-kidney axis, which is the complex
interplay between the intestinal and urinary tracts in human health and disease. A critical barrier to developing
new treatments for stone prevention is a lack of understanding of how perturbations of the gut microbiome and
downstream changes in metabolites in the intestinal and urinary tracts contribute to kidney stone disease.
In this proposal, we build on our recent discoveries of the role of diet, antibiotics, the gut microbiome, and the
metabolome in kidney stone disease. We leverage an interdisciplinary team that is uniquely poised to define the
human gut-kidney axis in kidney stone disease by combining expertise in using nutritional profiling, mediation
analyses of high-dimensional microbiome and metabolomic data, and large data analytics. The proposed
research tests the central hypothesis that diet and antibiotics contribute to nephrolithiasis by perturbing the gut-
kidney axis through alterations of the gut microbiome. In doing so, the proposed studies will identify metabolic
pathways in the gut-kidney axis that could be targets for novel therapeutics to prevent kidney stones. In Aim 1,
we will identify perturbations of the microbiome and metabolome in kidney stone disease. We will assess diet
and collect stool and urine from 300 participants ≥4 years old without recent antibiotic exposure (150 with calcium
kidney stones and 150 matched controls), oversampling younger participants. We will sequence the gut
microbiome using shotgun metagenomics and measure downstream metabolites using untargeted
metabolomics of stool and urine, targeted short-chain fatty acid metabolomics of stool, and 24-hour urine
chemistries. Using novel mediation models, we will define the direct and indirect effect of diet on the gut
microbiome and intestinal and urinary metabolites and its contribution to kidney stones. In Aim 2, we will, for the
first time, determine the relationship between oral antibiotic exposure and urine chemistries in kidney stone
disease. We will link 24-hour urine chemistry results with pharmaceutical claims and clinical data of individuals
in the HealthCore database, which includes >48 million individuals. We will conduct a nested case-control study
to determine the relationship between the dose and duration of antibiotic exposure and kidney stones and to
identify sub-groups at greatest risk. We will then perform a cohort study to identify how oral antibiotics alter urine
chemistries. These results will identify metabolites that contribute to kidney stones following perturbation of the
gut microbiome and provide key insights for future studies of primary and secondary stone prevention.
项目总结
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 }}
Michelle Denburg其他文献
Michelle Denburg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('Michelle Denburg', 18)}}的其他基金
Mentoring of Early Career Researchers from Diverse Backgrounds
指导来自不同背景的早期职业研究人员
- 批准号:
10797793 - 财政年份:2023
- 资助金额:
$ 72.65万 - 项目类别:
Evaluation of the gut-kidney axis in kidney stone disease
肾结石疾病中肠-肾轴的评估
- 批准号:
10133067 - 财政年份:2019
- 资助金额:
$ 72.65万 - 项目类别:
Evaluation of the gut-kidney axis in kidney stone disease
肾结石疾病中肠-肾轴的评估
- 批准号:
10385846 - 财政年份:2019
- 资助金额:
$ 72.65万 - 项目类别:
The impact of glomerular disorders on bone quality and strength
肾小球疾病对骨质量和强度的影响
- 批准号:
10452536 - 财政年份:2018
- 资助金额:
$ 72.65万 - 项目类别:
The impact of glomerular disorders on bone quality and strength
肾小球疾病对骨质量和强度的影响
- 批准号:
10226160 - 财政年份:2018
- 资助金额:
$ 72.65万 - 项目类别:
The impact of glomerular disorders on bone quality and strength
肾小球疾病对骨质量和强度的影响
- 批准号:
9789870 - 财政年份:2018
- 资助金额:
$ 72.65万 - 项目类别:
CHOP Pediatric Center of Excellence in Nephrology
CHOP 儿科肾病卓越中心
- 批准号:
10705295 - 财政年份:2017
- 资助金额:
$ 72.65万 - 项目类别:
CHOP Pediatric Center of Excellence in Nephrology
CHOP 儿科肾病卓越中心
- 批准号:
10529731 - 财政年份:2017
- 资助金额:
$ 72.65万 - 项目类别:
相似海外基金
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:
$ 72.65万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The impact of changes in social determinants of health on adolescent and young adult mental health during the COVID-19 pandemic: A longitudinal study of the Asenze cohort in South Africa
COVID-19 大流行期间健康社会决定因素的变化对青少年和年轻人心理健康的影响:南非 Asenze 队列的纵向研究
- 批准号:
10755168 - 财政年份:2023
- 资助金额:
$ 72.65万 - 项目类别:
A Priority Setting Partnership to Establish a Patient, Caregiver, and Clinician-identified Research Agenda for Adolescent and Young Adult Cancer in Canada
建立优先合作伙伴关系,以建立患者、护理人员和临床医生确定的加拿大青少年和年轻人癌症研究议程
- 批准号:
480840 - 财政年份:2023
- 资助金额:
$ 72.65万 - 项目类别:
Miscellaneous Programs
Incidence and Time on Onset of Cardiovascular Risk Factors and Cardiovascular Disease in Adult Survivors of Adolescent and Young Adult Cancer and Association with Exercise
青少年和青年癌症成年幸存者心血管危险因素和心血管疾病的发病率和时间以及与运动的关系
- 批准号:
10678157 - 财政年份:2023
- 资助金额:
$ 72.65万 - 项目类别:
Fertility experiences among ethnically diverse adolescent and young adult cancer survivors: A population-based study
不同种族青少年和年轻成年癌症幸存者的生育经历:一项基于人群的研究
- 批准号:
10744412 - 财政年份:2023
- 资助金额:
$ 72.65万 - 项目类别:
Treatment development for refractory leukemia using childhood/adolescent, and young adult leukemia biobank
利用儿童/青少年和青年白血病生物库开发难治性白血病的治疗方法
- 批准号:
23K07305 - 财政年份:2023
- 资助金额:
$ 72.65万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Molecular design of Two-Way Player CAR-T cells to overcome disease/antigen heterogeneity of childhood, adolescent, and young adult cancers
双向 CAR-T 细胞的分子设计,以克服儿童、青少年和年轻成人癌症的疾病/抗原异质性
- 批准号:
23H02874 - 财政年份:2023
- 资助金额:
$ 72.65万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Effects of adolescent social isolation on adult decision making and corticostriatal circuitry
青少年社会隔离对成人决策和皮质纹状体回路的影响
- 批准号:
10756652 - 财政年份:2023
- 资助金额:
$ 72.65万 - 项目类别:
Adolescent trauma produces enduring disruptions in sleep architecture that lead to increased risk for adult mental illness
青少年创伤会对睡眠结构产生持久的破坏,从而导致成人精神疾病的风险增加
- 批准号:
10730872 - 财政年份:2023
- 资助金额:
$ 72.65万 - 项目类别:
Using Tailored mHealth Strategies to Promote Weight Management among Adolescent and Young Adult Cancer Survivors
使用量身定制的移动健康策略促进青少年和年轻癌症幸存者的体重管理
- 批准号:
10650648 - 财政年份:2023
- 资助金额:
$ 72.65万 - 项目类别: