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A Novel Microbial Source of Stochasticity in Microbiota-Driven Diseases- [electronic resource]
A Novel Microbial Source of Stochasticity in Microbiota-Driven Diseases- [electronic resource]
상세정보
- 자료유형
- 학위논문(국외)
- 자관 청구기호
- 기본표목-개인명
- 표제와 책임표시사항
- A Novel Microbial Source of Stochasticity in Microbiota-Driven Diseases - [electronic resource] / Yi Yang
- 발행, 배포, 간사 사항
- 발행, 배포, 간사 사항
- 형태사항
- 1 online resource(p.106 )
- 일반주기
- Source: Dissertations Abstracts International, Volume: 85-01, Section: B.
- 일반주기
- Advisor: Palm, Noah W.
- 학위논문주기
- Thesis (Ph.D.)--Yale University, 2023.
- 이용제한주기
- This item must not be sold to any third party vendors.
- 요약 등 주기
- 요약Gut commensals with the capacity to translocate across the intestinal barrier can drive the development of diverse immune-mediated diseases. However, the key factors that dictate bacterial translocation remain unclear. Recent studies have revealed that gut microbiota strains can adapt and evolve throughout the lifetime of the host, raising the possibility that changes in individual commensals themselves over time may impact their propensity to elicit inflammatory disease. Here we show that within-host evolution of the model gut pathobiont Enterococcus gallinarum facilitates bacterial translocation and initiation of chronic inflammation. Using a combination of in vivo experimental evolution and comparative genomics, we found that E. gallinarum diverges into independent lineages adapted to colonize either luminal or mucosal niches in the gut. Compared to ancestral and luminal E. gallinarum, mucosally-adapted strains evade detection and clearance by the immune system, exhibit increased translocation to and survival within the mesenteric lymph nodes and liver, and initiate inflammatory responses in the intestine and liver. Mechanistically, these changes in bacterial behavior are associated with non-synonymous mutations or indels in defined regulatory genes in E. gallinarum, altered microbial gene expression programs, and remodeled cell wall structures. By extending to other commensal species, we found that Lactobacillus reuteri also exhibited broadly similar patterns of divergent evolution and enhanced immune evasion in a monocolonization-based model of within-host evolution. Overall, these studies define within-host evolution as a critical regulator of commensal pathogenicity that provides a unique source of stochasticity in the development and progression of microbiota-driven disease.
- 주제명부출표목-일반주제명
- 주제명부출표목-일반주제명
- 주제명부출표목-일반주제명
- 비통제 색인어
- 비통제 색인어
- 비통제 색인어
- 비통제 색인어
- 비통제 색인어
- 부출표목-단체명
- 기본자료저록
- Dissertations Abstracts International. 85-01B.
- 기본자료저록
- Dissertation Abstract International
- 전자적 위치 및 접속
- 원문정보보기
- 소장사항
-
202402 2024
MARC
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■006m o d
■007cr
■020 ▼a9798379778804
■035 ▼a(MiAaPQ)AAI30248660
■040 ▼aMiAaPQ▼cMiAaPQ
■08204▼a616.079▼222
■090 ▼a전자도서(박사논문)
■1001 ▼aYang, Yi.
■24512▼aA Novel Microbial Source of Stochasticity in Microbiota-Driven Diseases▼h[electronic resource]▼cYi Yang
■260 ▼a[S.l.]▼bYale University. ▼c2023
■260 1▼aAnn Arbor▼bProQuest Dissertations & Theses▼c2023
■300 ▼a1 online resource(p.106 )
■500 ▼aSource: Dissertations Abstracts International, Volume: 85-01, Section: B.
■500 ▼aAdvisor: Palm, Noah W.
■5021 ▼aThesis (Ph.D.)--Yale University, 2023.
■506 ▼aThis item must not be sold to any third party vendors.
■520 ▼aGut commensals with the capacity to translocate across the intestinal barrier can drive the development of diverse immune-mediated diseases. However, the key factors that dictate bacterial translocation remain unclear. Recent studies have revealed that gut microbiota strains can adapt and evolve throughout the lifetime of the host, raising the possibility that changes in individual commensals themselves over time may impact their propensity to elicit inflammatory disease. Here we show that within-host evolution of the model gut pathobiont Enterococcus gallinarum facilitates bacterial translocation and initiation of chronic inflammation. Using a combination of in vivo experimental evolution and comparative genomics, we found that E. gallinarum diverges into independent lineages adapted to colonize either luminal or mucosal niches in the gut. Compared to ancestral and luminal E. gallinarum, mucosally-adapted strains evade detection and clearance by the immune system, exhibit increased translocation to and survival within the mesenteric lymph nodes and liver, and initiate inflammatory responses in the intestine and liver. Mechanistically, these changes in bacterial behavior are associated with non-synonymous mutations or indels in defined regulatory genes in E. gallinarum, altered microbial gene expression programs, and remodeled cell wall structures. By extending to other commensal species, we found that Lactobacillus reuteri also exhibited broadly similar patterns of divergent evolution and enhanced immune evasion in a monocolonization-based model of within-host evolution. Overall, these studies define within-host evolution as a critical regulator of commensal pathogenicity that provides a unique source of stochasticity in the development and progression of microbiota-driven disease.
■590 ▼aSchool code: 0265.
■650 4▼aImmunology.
■650 4▼aMicrobiology.
■650 4▼aPathology.
■653 ▼aBacterial pathogenicity
■653 ▼aBacterial translocation
■653 ▼aCommensal microbes
■653 ▼aWithin-host evolution
■653 ▼aChronic inflammation
■690 ▼a0982
■690 ▼a0410
■690 ▼a0571
■71020▼aYale University▼bImmunobiology.
■7730 ▼tDissertations Abstracts International▼g85-01B.
■773 ▼tDissertation Abstract International
■790 ▼a0265
■791 ▼aPh.D.
■792 ▼a2023
■793 ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T16931326▼nKERIS▼z이 자료의 원문은 한국교육학술정보원에서 제공합니다.
■980 ▼a202402▼f2024
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