Changes in Enteric Microbiota and Inflammation with HIV PrEP
Changes in Enteric Microbiota and Inflammation with HIV PrEP
批准号:
10700595
负责人:
Brandon Swartz Maust
金额:
$19.36万
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-09-01 至 2028-08-31
关键词:
AIDS preventionAcquired Immunodeficiency SyndromeAddressAffectAnti-Inflammatory AgentsAnti-Retroviral AgentsAntibioticsAreaAwardBacteriaBacteriophagesBiometryBloodBlood specimenCareer MobilityCellsChildClostridium difficileClustered Regularly Interspaced Short Palindromic RepeatsCommunitiesComputational BiologyControl GroupsDNADevelopmentDevelopment PlansDiseaseEnrollmentEnteralEpithelial CellsEpitheliumFecesFumaratesFunctional disorderFutureGenerationsGenesGoalsGrowthHIVHIV InfectionsHealthHumanImmuneImmune systemImmunityIn VitroIncidenceIndividualInfectionInflammationInflammatoryInterventionIntestinesLiteratureMeasuresMedicineMetagenomicsMethodsModelingMucositisMusNucleosidesNutritionalOrganismParticipantPathogenicityPersonsPhysiciansPopulationPredatory BehaviorPredispositionProbioticsProkaryotic CellsProphagesRNA SequencesResearchResourcesReverse Transcriptase InhibitorsRisk FactorsRisk ReductionSafetySamplingScientistSeriesShapesShotgun SequencingSignal TransductionSpecimenStructureTechniquesTenofovirTestingTherapeutic InterventionTrainingUlcerative ColitisValidationViralViral GenomeVirionVirusVisitbacterial communitybacteriomecareer developmentcohortdysbiosisemtricitabineenteric dysbiosisexperimental studyglobal healthgut inflammationgut microbiotaimprovedinflammatory markermembermetagenomemetagenomic sequencingmicrobialmicrobicidemicrobiomemicrobiotamicroorganism interactionmultiple omicsnovelparticlepathobiontpre-exposure prophylaxisprebioticspreventresponsestool samplesymbiontsystemic inflammatory responseviromevolunteer
中文摘要
项目总结/文摘
英文摘要
PROJECT SUMMARY/ABSTRACT
Although HIV remains a major global health problem, strategies such as Pre-Exposure Prophylaxis (PrEP) can
reduce the incidence of new infections. However, the antiretrovirals used for HIV prevention have been
associated with increased enteric inflammation in individuals using them. We hypothesize that their broad activity
affects both the viral and bacterial communities of the gut, causing local inflammation which may cause epithelial
dysfunction and increase microbial translocation and systemic inflammation.
We propose a series of metagenomic experiments to characterize the inflammatory contributions of intestinal
viruses and bacteria and their changes with PrEP. For this novel research, we must first enroll a cohort of
participants starting HIV PrEP and a similar group of control participants not using PrEP. We will collect blood
and stool samples at baseline and after three months. First, we will characterize the virome fromstool specimens
using metagenomic sequencing of filtered viral particles and compare the changes of within- and between-
individual diversity in the participants on PrEP and those in the control group (aim 1). Next, we will use
metagenomic sequencing to characterize stool bacterial populations, including prophages (aim 2). We will
computationally predict bacterial targets of bacteriophages, then culture the identified virus-bacterial pairs from
participant specimens. Using these cultures, we will validate the predicted interactions and assess the ability of
PrEP to disrupt them. Finally, we will measure inflammatory markers in stool and blood and use the viral and
bacterial abundances to identify which organisms are most strongly associated with inflammation (aim 3). These
experiments will identify viruses and bacteria which interact with each other and with PrEP and define their
impact on host inflammation.
Dr. Maust’s career development plan builds on his background in computational biology, and lab expertise in
analyzing bacterial communities by marker gene sequencing and adds training in metagenomic sequencing,
biostatistical techniques, and methods for viral and bacterial culture. This K08 award is a well-structured way for
him to make maximal use of UW and Seattle Children’s extensive scientific resources to achieve independence
as a physician scientist, advancing his career goal to understand microbial interactions as they impact host
immunity to guide therapeutic interventions.
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