Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria

被引：986

作者：

Dejea, Christine M. ^{[1
,2
,9
]}

Fathi, Payam ^{[1
,2
,3
,10
]}

Craig, John M. ^{[4
]}

Boleij, Annemarie ^{[1
,5
]}

Taddese, Rahwa ^{[5
]}

Geis, Abby L. ^{[1
,2
,11
]}

Wu, Xinqun ^{[1
,3
]}

Shields, Christina E. DeStefano ^{[1
,2
]}

Hechenbleikner, Elizabeth M. ^{[6
,12
]}

Huso, David L. ^{[7
]}

Anders, Robert A. ^{[8
]}

Giardiello, Francis M. ^{[2
,3
]}

Wick, Elizabeth C. ^{[6
,13
]}

Wang, Hao ^{[1
,2
]}

Wu, Shaoguang ^{[1
,3
]}

Pardoll, Drew M. ^{[1
,2
]}

Housseau, Franck ^{[1
,2
]}

Sears, Cynthia L. ^{[1
,2
,3
]}

机构：

[1] Johns Hopkins Univ, Bloomberg Kimmel Inst Canc Immunotherapy, Baltimore, MD 21218 USA

[2] Johns Hopkins Univ, Dept Oncol, Baltimore, MD 21218 USA

[3] Johns Hopkins Univ, Dept Med, Baltimore, MD 21218 USA

[4] Johns Hopkins Univ, Dept Environm Hlth Sci, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA

[5] Radboud Univ Nijmegen, Dept Pathol, Med Ctr, Postbus 9101, NL-6500 HB Nijmegen, Netherlands

[6] Johns Hopkins Univ, Dept Surg, Baltimore, MD USA

[7] Johns Hopkins Univ, Dept Mol & Comparat Pathobiol, Baltimore, MD USA

[8] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA

[9] 10903 New Hampshire Ave,WO22 RM 5171, Silver Spring, MD 20993 USA

[10] Vanderbilt Univ, Sch Med, 340 Light Hall, Nashville, TN 37232 USA

[11] Arkansas Coll Osteopath Med, 7000 Chad Colley Blvd, Ft Smith, AR 72916 USA

[12] Mt Sinai Hosp, Dept Surg, 5 East 98th St, New York, NY 10029 USA

[13] Univ Calif San Francisco, Dept Surg, 513 Parnassus Ave,S 549, San Francisco, CA 94143 USA

来源：

SCIENCE | 2018年 / 359卷 / 6375期

关键词：

INFLAMMATORY-BOWEL-DISEASE; CANCER; GENE; MICROBIOTA; MUCOSA;

D O I：

10.1126/science.aah3648

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Individuals with sporadic colorectal cancer (CRC) frequently harbor abnormalities in the composition of the gut microbiome; however, the microbiota associated with precancerous lesions in hereditary CRC remains largely unknown. We studied colonic mucosa of patients with familial adenomatous polyposis (FAP), who develop benign precursor lesions (polyps) early in life. We identified patchy bacterial biofilms composed predominately of Escherichia coli and Bacteroides fragilis. Genes for colibactin (clbB) and Bacteroides fragilis toxin (bft), encoding secreted oncotoxins, were highly enriched in FAP patients' colonic mucosa compared to healthy individuals. Tumor-prone mice cocolonized with E. coli (expressing colibactin), and enterotoxigenic B. fragilis showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacterial strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.

引用

页码：592 / +

页数：6

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