What can gut bacteria tell us about colorectal cancer?

Abstract

*Department of Laboratory Medicine (830), Nijmegen Institute for Infection, Inflammation & Immunity (N4i) and Radboud University Centre for Oncology (RUCO), Radboud University Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands; Tel.: +31 24 3618947; Fax: +31 24 3541743; h.tjalsma@labgk.umcn.nl One of the salient features of colonic malignancies is their continuous physical interaction with a dense bacterial population that consists of more than 10 different species [1,2]. In this respect, it may not sound so surprising that both clinical studies and experimental models have directly or indirectly linked the intestinal microbiota, or specific members thereof, to the development of colorectal cancer (CRC) [3]. Several types of evidence provide important information on the impact of host–microbiota interactions during disease development. First, the high bacterial density in the large intestine (~10 cells/ml) compared with the small intestine (~10 cells/ml), is paralleled by an approximate 12-fold increase in cancer incidence in the human colon [4]. Second, inflammatory bowel disease (IBD) patients with a reduced intestinal barrier function, who are thus associated with increased intestinal exposure to microbes, have an approximate fivefold increased risk for CRC [5]. Third, clinical studies have shown that the use of NSAIDs can reduce human CRC by as much as 75% [6]. Fourth, mice that are genetically susceptible to CRC develop significantly less tumors under germ-free conditions [7]. Fifth, it has been shown that toxins from specific gut bacteria can induce DNA damage and increase inflammation, cell proliferation and cancer progression [8,9]. Sixth, bacterial metabolism can generate oxygen radicals that induce DNA damage and chromosomal instability [10]. Seventh, bacterial metabolism of dietary factors was shown to result in the formation of genotoxins and carcinogens [3,11]. Finally, certain infections with opportunistic gut pathogens are s pecifically associated with human CRC [12].