Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria.
Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria.
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DOI：
10.1126/science.aah3648
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发表时间：
2018-02-02
期刊：
影响因子：
--
通讯作者：
Sears CL
中科院分区：
文献类型：
--
作者：
Dejea CM;Fathi P;Craig JM;Boleij A;Taddese R;Geis AL;Wu X;DeStefano Shields CE;Hechenbleikner EM;Huso DL;Anders RA;Giardiello FM;Wick EC;Wang H;Wu S;Pardoll DM;Housseau F;Sears CL
散发性结直肠癌(CRC)患者经常存在肠道微生物组的异常；然而，遗传性结直肠癌癌前病变相关的微生物群在很大程度上仍不清楚。我们研究了家族性腺瘤性息肉病(FAP)患者的结肠粘膜，这些患者在生命早期就发展为良性前驱病变(息肉)。我们鉴定了主要由大肠杆菌和脆弱类杆菌组成的片状细菌生物膜。与正常人相比，FAP患者结肠粘膜中编码分泌型癌毒素的结肠肌蛋白(ClbB)和脆弱类杆菌毒素(BFT)基因高度丰富。与单独使用任何一种细菌的小鼠相比，与大肠杆菌(表达Colibactin)和产肠毒素脆弱芽孢杆菌共定居的易患肿瘤的小鼠显示出结肠中IL-17增加和结肠上皮DNA损伤，肿瘤发生更快，死亡率更高。这些数据表明，结肠早期肿瘤和致癌细菌之间存在意想不到的联系。
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.
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影响因子：
24.5
作者：
Swidsinski, Alexander;Loening-Baucke, Vera;Doerffel, Yvonne
通讯作者：
Doerffel, Yvonne
影响因子：
3.7
作者：
Son JS;Khair S;Pettet DW 3rd;Ouyang N;Tian X;Zhang Y;Zhu W;Mackenzie GG;Robertson CE;Ir D;Frank DN;Rigas B;Li E
通讯作者：
Li E
影响因子：
29
作者：
Johnson CH;Dejea CM;Edler D;Hoang LT;Santidrian AF;Felding BH;Ivanisevic J;Cho K;Wick EC;Hechenbleikner EM;Uritboonthai W;Goetz L;Casero RA Jr;Pardoll DM;White JR;Patti GJ;Sears CL;Siuzdak G
通讯作者：
Siuzdak G
DOI：
10.1126/science.1224820
发表时间：
2012-10-05
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Arthur JC;Perez-Chanona E;Mühlbauer M;Tomkovich S;Uronis JM;Fan TJ;Campbell BJ;Abujamel T;Dogan B;Rogers AB;Rhodes JM;Stintzi A;Simpson KW;Hansen JJ;Keku TO;Fodor AA;Jobin C
通讯作者：
Jobin C
影响因子：
11.8
作者：
Prindiville TP;Sheikh RA;Cohen SH;Tang YJ;Cantrell MC;Silva J Jr
通讯作者：
Silva J Jr