The human bowel contains a large and dynamic bacterial population that is not only essential for intestinal health, but also critical for the development of diseases such as cancer. In this respect, the Gram-positive bacterium Streptococcus bovis has been associated with colon cancer for many years. To investigate the clinical importance of this association, an immunocapture mass spectrometry assay was developed that can generate infection-related protein profiles. The composition of these profiles is governed by the capture of specific antigens by serum antibodies from colon cancer patients. This assay showed that S. bovis antigen profiles could distinguish 11 out of 12 colon cancer patients from 8 control subjects, whereas antigen profiles derived from the gut bacterium Escherichia coli were not diagnostic for colon cancer. Moreover, S. bovis antigen profiles were also detected in polyp patients, indicating that infection with this bacterium does occur early during carcinogenesis. Highly accurate tandem mass spectrometry was used to identify one of the diagnostic antigens as a surface-exposed heparin-binding protein, which might be involved in attachment of S. bovis to tumor cells. Together, these findings corroborate the hypothesis that colonic lesions provide a specific niche for S. bovis, resulting in tumor-associated ''silent'' infections. These infections, however, only become apparent in colon cancer patients with a compromised immune system (bacteremia) or coincidental cardiac valve lesions (endocarditis). This makes profiling of the humoral immune response against ''silent'' S. bovis infections a promising diagnostic tool for the early detection of human colon cancer, which is crucial for the effective treatment of this disease. ' 2006 Wiley-Liss, Inc.
Key words: colon cancer; early detection; diagnostic bacterial antigens; Streptococcus bovisThe human bowel is the natural habitat for a large and dynamic bacterial community, which is essential for the control of intestinal epithelial homeostasis and human health.1,2 However, gut flora might also be an essential factor in certain diseases, including multisystem organ failure, inflammatory bowel diseases, and colon cancer.3 Although bacterial infections were originally not considered to be a major cause of cancer, accumulating evidence suggests that bacteria can induce or promote cancer by inflammation. In this model, tumor formation is caused or promoted by induction of cell proliferation and the production of mutagenic free radicals and n-nitroso compounds. In this respect, Helicobacter pylori has been the first invasive bacterium to be identified as a definite cause of gastric cancer. 4 Similarly, an association between Streptococcus bovis infection and colon cancer has been known for at least 25 years. Moreover, recent research has shown that S. bovis can promote intestinal carcinogenesis in a rat model for colon cancer.6 Certain cell surface proteins of this bacterium can induce inflammation, supporting a linkage between S. bovis, inflammation and ...