Critical functions of the gut microbiota that mediate recovery from recurrent Clostridium difficile infection
肠道微生物群介导复发性艰难梭菌感染恢复的关键功能
基本信息
- 批准号:10396013
- 负责人:
- 金额:$ 15.35万
- 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
- 起止时间:2018-05-04 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:AffectBacteriaBile AcidsBioinformaticsButyratesClostridium difficileCommunicable DiseasesCommunitiesComplementDevelopmentDiarrheaDiseaseDisease modelEcologyEcosystemEnvironmentFecesFosteringFundingGastrointestinal tract structureGerm-FreeGoalsGrowthHealthHealth Care CostsHealthcareHumanInfectionKnowledgeLinkMediatingMentorsMentorshipMetabolicMetabolic PathwayMetagenomicsMethodsMicrobeMissionModelingMusOutcomePathway interactionsPatient CarePatientsPreventionPrimary InfectionProductionRecoveryRecurrenceRecurrent diseaseResearchResearch PersonnelResistanceStructureTestingTherapeuticTrainingUnited StatesUnited States National Institutes of HealthVolatile Fatty Acidsbasecare costscareerclinically relevantcolonization resistanceeffective therapyfecal transplantationgut microbiotahealthcare-associated infectionshuman microbiotahumanized mouseimprovedinnovationmethod developmentmicrobialmicrobial communitymicrobial compositionmicrobiotamouse modelnovelpathogenpreventrRNA Genesrecurrent infectionskillssuccesstranslational scientisttransplantation therapy
项目摘要
ABSTRACT
Recurrent Clostridium difficile infection (CDI) affects 20-30% of patients following successful treatment of an
initial disease episode. It is hypothesized that the gut microbiota, the microbial community within the
gastrointestinal tract, is involved in the development of and recovery from recurrence. Microbial-based
treatments that promote the growth of `healthy' bacteria, such as fecal microbiota transplantation (FMT), have
emerged as an effective treatment method for recurrent CDI. Nevertheless, there is a fundamental lack of
knowledge of the microbes responsible for functions that contribute to colonization resistance against C.
difficile. We have characterized a murine model of recurrent infection, and observed that murine fecal material
from healthy mice is capable of mediating efficient clearance of C. difficile. Previous studies using germ-free
mice have successfully established colonization resistance against C. difficile with human microbiota. Contrary
to this, we observed that FMT from healthy humans did not resolve CDI in our model. While both FMT
treatments changed the microbiota composition, we observed deficient levels of several metabolites. Our
mouse model of recurrent CDI provides us with a method to understand how community structures assemble
to provide colonization resistance against CDI, enabling us to differentiate the critical microbial features in
colonization resistance against C. difficile. We hypothesize that the metabolic environment that limits C. difficile
colonization and growth is dependent on the assembly of succinct microbiota communities. The scientific
objective of this proposal is to elucidate the link between the structure and function of a microbial community
capable of mediating resistance to or recovery from CDI. We aim to do this using the following specific aims: 1)
define structural features in microbial communities that mediate colonization resistance to C. difficile and 2)
identify metabolic pathways in microbial communities that resolve CDI. The training objective of this proposal is
to complement the trainee's background in microbial ecology with bioinformatic and experimental skills that
focus on functions of microbial communities to support transition of the candidate into an independent,
translational investigator. Completion of these aims will result in more comprehensive knowledge of how
microbes function to provide colonization resistance, aiding the critical need to prevent or treat CDI, an
important healthcare-associated infection. In conjunction with the exceptional mentoring team and institutional
environment, this proposal will provide the candidate with scientific skills and career mentorship to become an
independent investigator in an inter-disciplinary field encompassing both microbial ecology and infectious
disease.
摘要
项目成果
期刊论文数量(9)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Multiomics Profiling Reveals Signatures of Dysmetabolism in Urban Populations in Central India.
- DOI:10.3390/microorganisms9071485
- 发表时间:2021-07-12
- 期刊:
- 影响因子:4.5
- 作者:Monaghan TM;Biswas RN;Nashine RR;Joshi SS;Mullish BH;Seekatz AM;Blanco JM;McDonald JAK;Marchesi JR;Yau TO;Christodoulou N;Hatziapostolou M;Pucic-Bakovic M;Vuckovic F;Klicek F;Lauc G;Xue N;Dottorini T;Ambalkar S;Satav A;Polytarchou C;Acharjee A;Kashyap RS
- 通讯作者:Kashyap RS
Dilution as a Solution: Targeting Microbial Populations with a Simplified Dilution Strategy.
稀释作为解决方案:通过简化的稀释策略针对微生物种群。
- DOI:10.1128/msphere.00701-20
- 发表时间:2020
- 期刊:
- 影响因子:4.8
- 作者:Bhattacharjee,Disha;Seekatz,AnnaM
- 通讯作者:Seekatz,AnnaM
Diversity and Prevalence of Clostridium innocuum in the Human Gut Microbiota.
- DOI:10.1128/msphere.00569-22
- 发表时间:2023-02-21
- 期刊:
- 影响因子:4.8
- 作者:
- 通讯作者:
Butyrate enhances Clostridioides difficile sporulation in vitro.
- DOI:10.1128/jb.00138-23
- 发表时间:2023-09-26
- 期刊:
- 影响因子:3.2
- 作者:Baldassare, Michelle A.;Bhattacharjee, Disha;Coles, Julian D.;Nelson, Sydney;Mccollum, C. Alexis;Seekatz, Anna M.
- 通讯作者:Seekatz, Anna M.
The role of the gut microbiome in colonization resistance and recurrent Clostridioides difficile infection.
- DOI:10.1177/17562848221134396
- 发表时间:2022
- 期刊:
- 影响因子:4.2
- 作者:Seekatz, Anna Maria;Safdar, Nasia;Khanna, Sahil
- 通讯作者:Khanna, Sahil
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Anna Maria Seekatz其他文献
Anna Maria Seekatz的其他文献
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{{ truncateString('Anna Maria Seekatz', 18)}}的其他基金
Niche Partitioning of Commensal Clostridia in the Gut
肠道共生梭菌的生态位划分
- 批准号:
10713512 - 财政年份:2023
- 资助金额:
$ 15.35万 - 项目类别:
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