[DEBUG-WINDOW 처리영역 보기]
즐겨찾기  |  뉴스레터  |  오늘의 정보 회원가입   로그인
BRIC홈 한국을 빛내는 사람들
대학원 진학 설문조사
스폰서배너광고 안내  배너1 배너2
전체보기 추천논문 상위피인용논문 인터뷰 그이후 한빛사통계
사진없음
홍보영 (Bo-Young Hong) 저자 이메일 보기
UConn Health, Jackson Laboratory for Genomic Medicine
조회 217  인쇄하기 주소복사 트위터 공유 페이스북 공유 
Chemotherapy-induced oral mucositis is associated with detrimental bacterial dysbiosis
열기 Authors and Affiliations

Abstract

Background
Gastrointestinal mucosal injury (mucositis), commonly affecting the oral cavity, is a clinically significant yet incompletely understood complication of cancer chemotherapy. Although antineoplastic cytotoxicity constitutes the primary injury trigger, the interaction of oral microbial commensals with mucosal tissues could modify the response. It is not clear, however, whether chemotherapy and its associated treatments affect oral microbial communities disrupting the homeostatic balance between resident microorganisms and the adjacent mucosa and if such alterations are associated with mucositis. To gain knowledge on the pathophysiology of oral mucositis, 49 subjects receiving 5-fluorouracil (5-FU) or doxorubicin-based chemotherapy were evaluated longitudinally during one cycle, assessing clinical outcomes, bacterial and fungal oral microbiome changes, and epithelial transcriptome responses. As a control for microbiome stability, 30 non-cancer subjects were longitudinally assessed. Through complementary in vitro assays, we also evaluated the antibacterial potential of 5-FU on oral microorganisms and the interaction of commensals with oral epithelial tissues.

Results
Oral mucositis severity was associated with 5-FU, increased salivary flow, and higher oral granulocyte counts. The oral bacteriome was disrupted during chemotherapy and while antibiotic and acid inhibitor intake contributed to these changes, bacteriome disruptions were also correlated with antineoplastics and independently and strongly associated with oral mucositis severity. Mucositis-associated bacteriome shifts included depletion of common health-associated commensals from the genera Streptococcus, Actinomyces, Gemella, Granulicatella, and Veillonella and enrichment of Gram-negative bacteria such as Fusobacterium nucleatum and Prevotella oris. Shifts could not be explained by a direct antibacterial effect of 5-FU, but rather resembled the inflammation-associated dysbiotic shifts seen in other oral conditions. Epithelial transcriptional responses during chemotherapy included upregulation of genes involved in innate immunity and apoptosis. Using a multilayer epithelial construct, we show mucositis-associated dysbiotic shifts may contribute to aggravate mucosal damage since the mucositis-depleted Streptococcus salivarius was tolerated as a commensal, while the mucositis-enriched F. nucleatum displayed pro-inflammatory and pro-apoptotic capacity.

Conclusions
Altogether, our work reveals that chemotherapy-induced oral mucositis is associated with bacterial dysbiosis and demonstrates the potential for dysbiotic shifts to aggravate antineoplastic-induced epithelial injury. These findings suggest that control of oral bacterial dysbiosis could represent a novel preventive approach to ameliorate oral mucositis.

Keywords : Microbiome, Cancer, Chemotherapy, Oral mucositis, Mucosal-microbial crosstalk

논문정보
- 형식: Research article
- 게재일: 2019년 04월 (BRIC 등록일 2019-05-03)
- 연구진: 국외연구진
- 분야: Microbiology
  댓글 0
등록
 
목록
동일바이오테크
관련링크
홍보영 님 전체논문보기 >
관련분야 논문보기
Microbiology

외부링크
Google (by Bo-Young Hong)
Pubmed (by Bo-Young Hong)
프리미엄 Bio일정 Bio일정 프리미엄 안내
의료기기 GMP의 이해과정(재직자 과정)
의료기기 GMP의 이해과정(재직자 과정)
날짜: 2019.06.18~20
장소: 경기도 성남시 분당구 판교로289번길 20 스타트업캠퍼스 2층 세미나실2
제6회 KXA(대한 이종이식 연구회) 심포지엄
제6회 KXA(대한 이종이식 연구회) 심포지엄
날짜: 2019.05.30
장소: 서울대학교 의과대학 삼성암연구동 2층 이건희홀
비임상시험 계획서 및 보고서 Review 과정(재직자 과정)
비임상시험 계획서 및 보고서 Review 과정(재직자 과정)
날짜: 2019.05.29~31
장소: 경기도 성남시 분당구 판교로289번길 20 스타트업캠퍼스 2층 세미나실1
위로가기
한빛사 홈  |  한빛사FAQ  |  한빛사 문의 및 제안
 |  BRIC소개  |  이용안내  |  이용약관  |  개인정보처리방침  |  이메일무단수집거부
Copyright © BRIC. All rights reserved.  |  문의 member@ibric.org
트위터 트위터    페이스북 페이스북   유튜브 유튜브    RSS서비스 RSS
에펜도르프코리아