Department of Laboratory Medicine, Nijmegen Institute for Infection, Inflammation and Immunity (N4i) & Radboud University Centre for Oncology (RUCO) of the Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, the Netherlands.
Biol Rev Camb Philos Soc. 2012 Aug;87(3):701-30. doi: 10.1111/j.1469-185X.2012.00218.x. Epub 2012 Feb 2.
A healthy human body contains at least tenfold more bacterial cells than human cells and the most abundant and diverse microbial community resides in the intestinal tract. Intestinal health is not only maintained by the human intestine itself and by dietary factors, but is also largely supported by this resident microbial community. Conversely, however, a large body of evidence supports a relationship between bacteria, bacterial activities and human colorectal cancer. Symbiosis in this multifaceted organ is thus crucial to maintain a healthy balance within the host-diet-microbiota triangle and accordingly, changes in any of these three factors may drive a healthy situation into a state of disease. In this review, the factors that sustain health or drive this complex intestinal system into dysbiosis are discussed. Emphasis is on the role of the intestinal microbiota and related mechanisms that can drive the initiation and progression of sporadic colorectal cancer (CRC). These mechanisms comprise the induction of pro-inflammatory and pro-carcinogenic pathways in epithelial cells as well as the production of (geno)toxins and the conversion of pro-carcinogenic dietary factors into carcinogens. A thorough understanding of these processes will provide leads for future research and may ultimately aid in development of new strategies for CRC diagnosis and prevention.
健康人体中含有的细菌细胞至少是人体细胞的十倍,而数量最多、种类最多的微生物群落存在于肠道中。肠道健康不仅由人类肠道本身和饮食因素维持,而且在很大程度上还依赖于这个常驻微生物群落。然而,大量证据表明,细菌、细菌活动与人类结直肠癌之间存在关联。因此,在这个多层面的器官中,共生对于在宿主-饮食-微生物三角关系中保持健康平衡至关重要,因此,这三个因素中的任何一个变化都可能将健康状况推向疾病状态。在这篇综述中,讨论了维持健康或促使这个复杂的肠道系统发生功能障碍的因素。重点是肠道微生物群及其相关机制在驱动散发性结直肠癌(CRC)的发生和进展中的作用。这些机制包括在肠上皮细胞中诱导促炎和致癌途径,以及产生(基因)毒素和将致癌饮食因素转化为致癌物质。对这些过程的深入了解将为未来的研究提供线索,并可能最终有助于开发结直肠癌诊断和预防的新策略。