By means of various experimental models (chemoprevention, tumour implantation in peritoneum and muscle tissue, Min mice model) it was observed that dietary administration of prebiotics (inulin, oligofructose) significantly reduced the processes of carcinogenesis and tumorigenesis.
With probiotics, too, there are some reports of anticarcinogenic properties. In one experiment it was observed that a combination of pre- and probiotic had synergistic anticarcinogenic activity.
In present biomarker project, it will be investigated whether these food ingredients have the potential to reduce carcinogenesis in human volunteers too.
The project addresses the important problem of the high rate of colorectal cancer (CRC) in Europe. The main aim is to evaluate whether the administration of synbiotics (a combination of pro- and prebiotics) to the diet of human volunteers can reduce the risk of colorectal cancer. The objective will be achieved by:
- In vitro studies that will identify the synbiotic combination with the greatest competitive advantage in the colonic ecosystem;
- Establishing the anticarcinogenic effect of this synbiotic, but also of the prebiotic and probiotics separately, by measuring tumour development in a long term (33w) rat colon cancer model;
- Refining a range of novel biomarkers for CRC in blood, faecal water and biopsies (tumour vs. healthy tissue);
- Evaluating in human subjects with a history (operated CRC patients) or predisposition for CRC (polypectomised patients) the potential of synbiotics to reduce the risk for CRC
The results from the project will contribute to the formulation of improved dietary advice for Europeans to reduce their risk for CRC.
The biomarker network was established: several parameters were evaluated for their use as a CRC biomarker. Currently, mRNA levels of different enzymes involved in the cancer process, in vitro tumour promoting activity and metastatic activity, calprotectin, GST š and cyclo oxygenase 2 activity, DNA damage, short chain fatty acids and several immunological parameters are measured in faeces and faecal water, in biopsy samples and in blood.
The synbiotic composition chosen as a daily dose for the SYNCAN human study was 10 g RAFTILOSE® Synergy 1 (enriched inulin mixture) as prebiotic and two types of health promoting bacteria as probiotic:1010 cfu/g Lactobacillus rhamnosus (LGG) and 1010 cfu/g Bifidobacterium lactis (Bb12).
The dietary interventions have started (placebo and synbiotic). They last 12 weeks in a parallel study design. Blood and faeces are sampled at regular intervals and biopsies are sampled at the beginning and the end of the intervention period. They are forwarded to the the biomarker network for further analysis
By means of an experimental model in which CRC is induced in rats, the SYNCAN has investigated the biological events. Preliminary results indicate that synbiotic and prebiotic treatment significantly reduce the number of tumours in the rat colon. Faecal, blood and tumour tissue are currently being analysed by the biomarker network in order to obtain understanding of the mechanisms involved in the anticarcinogenic activity of pre- and synbiotics.
The wealth of techniques and methods developed and evaluated during the first year of the SYNCAN project provides a firm basis for examining the mechanisms of colon cancer development and the protection against it by synbiotics in the diet. The biomarkers used could provide novel clinical markers to be used in oncology and further elaborate the understanding of the causes and treatment of CRC.