Assistant Professor

Laboratory Medicine

Nijmegen Institute for Infection, Inflammation & Immunity (N4i)

Radboud University Nijmegen Medical Center (Nijmegen, Netherlands)

Bacterial Infection & Colon Cancer

Accumulating evidence suggests that intestinal bacteria may be involved in the progression of colon cancer. However, Streptococcus bovis is one of the few gut bacteria the infection of which has a well-known clinical association with this disease. In addition, its bowel colonisation is increased in colon cancer patients. It was recently shown that the occurrence of antibodies against S. bovis proteins are prevalent in colon cancer patients and thereby may aid in the early diagnosis of this disease. This indicates that due to its relative low virulence, S. bovis infections remain in most cases clinically silent and can only be detected by molecular approaches. Only in a very small number of patients (<3%) that have co-incidental cardiac valve lesions (endocarditis) or a compromised immune system (bacteraemia) such infections can become eventually clinically apparent.

Based on these findings, diagnostic tests for the detection of S. bovis antibody expression in colon cancer patients are being developed for evaluation in clinical studies. Furthermore, in vitro interactions between gut bacteria and colon tumour cells are investigated as specific tumour cell responses may reveal additional diagnostic or prognostic markers for colon cancer and may provide new clues about the involvement of intestinal bacteria in colon cancer progression. As bacterial surface proteins are both vital mediators of adherence to epithelial cells and also important targets of the humoral immune system, another aim is the comprehensive profiling of the bacterial exoproteome.

Withholding iron from potential pathogens is an important host defense strategy against bacterial infection. A key mediator in this process is the iron regulatory peptide hormone hepcidin. Upon bacterial infection, liver cells secrete induced amounts of this peptide into the blood stream which causes iron to be retained in macrophages and intestinal iron absorption to be decreased by blocking the sole iron exporter ferroportin. Together this limits the iron available for extracellular bacterial growth. Ironically, however, this defense strategy increases intracellular iron pools which facilitates the growth of intracellular pathogens that escape lysosomal degradation after phagocytosis by macrophages. Strikingly, also colon tumor cells may accumulate intracellular iron in a hepcidin-dependend manner, thereby providing a potential niche for intracellular survival of bacterial gut-derived pathogens.

To gain further insight in the role of hepcidin in human iron metabolism during healthy and diseased states, a quantitative assay was developed exploiting sensitive time-of-flight mass spectrometry. This assay is now available as a service to the scientific community (www.hepcidinanalysis.com).

2008-present Co-founder and Managing Director of Hepcidinanalysis.com

2006-2010 Proteomic Exploration of Colon Cancer-associated Bacterial Infections to Reveal Molecular Tools for Cancer Detection, Prevention and Treatment (Dutch Cancer Association [KWF]: KUN 2006-3591)