Johnson Caroline H, Dejea Christine M, Edler David, Hoang Linh T, Santidrian Antonio F, Felding Brunhilde H, Ivanisevic Julijana, Cho Kevin, Wick Elizabeth C, Hechenbleikner Elizabeth M, Uritboonthai Winnie, Goetz Laura, Casero Robert A, Pardoll Drew M, White James R, Patti Gary J, Sears Cynthia L, Siuzdak Gary
Scripps Center for Metabolomics and Mass Spectrometry, The Scripps Research Institute, La Jolla, CA 92037, USA.
Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins Medical Institutions, Baltimore, MD 21218, USA.
Cell Metab. 2015 Jun 2;21(6):891-7. doi: 10.1016/j.cmet.2015.04.011. Epub 2015 May 7.
Bacterial biofilms in the colon alter the host tissue microenvironment. A role for biofilms in colon cancer metabolism has been suggested but to date has not been evaluated. Using metabolomics, we investigated the metabolic influence that microbial biofilms have on colon tissues and the related occurrence of cancer. Patient-matched colon cancers and histologically normal tissues, with or without biofilms, were examined. We show the upregulation of polyamine metabolites in tissues from cancer hosts with significant enhancement of N(1), N(12)-diacetylspermine in both biofilm-positive cancer and normal tissues. Antibiotic treatment, which cleared biofilms, decreased N(1), N(12)-diacetylspermine levels to those seen in biofilm-negative tissues, indicating that host cancer and bacterial biofilm structures contribute to the polyamine metabolite pool. These results show that colonic mucosal biofilms alter the cancer metabolome to produce a regulator of cellular proliferation and colon cancer growth potentially affecting cancer development and progression.
结肠中的细菌生物膜会改变宿主组织微环境。生物膜在结肠癌代谢中的作用已被提出,但迄今为止尚未得到评估。我们使用代谢组学方法,研究了微生物生物膜对结肠组织的代谢影响以及癌症的相关发生情况。对有或没有生物膜的患者匹配的结肠癌组织和组织学正常组织进行了检查。我们发现,癌症宿主组织中的多胺代谢产物上调,在生物膜阳性的癌症组织和正常组织中,N(1),N(12)-二乙酰精胺均显著增加。清除生物膜的抗生素治疗将N(1),N(12)-二乙酰精胺水平降低至生物膜阴性组织中的水平,这表明宿主癌症和细菌生物膜结构对多胺代谢产物池有贡献。这些结果表明,结肠黏膜生物膜会改变癌症代谢组,产生一种细胞增殖和结肠癌生长的调节剂,可能影响癌症的发生和发展。