Supervisors info:
Περικής Φούκας, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Ιωάννης Γ. Παναγιωτίδης, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Αδαμαντίνη Κυριακού, Αναπληρώτρια Καθηγήτρια, Τμήμα Επιστήμης Διαιτολογίας-Διατροφής, Χαροκόπειο Πανεπιστήμιο Αθηνών
Summary:
The emergence of new cases of colon cancer seems to have risen in recent years. This type of cancer is known as the second and third most frequently recorded disease worldwide in women and men respectively. The causes of the development of intestinal neoplasms are due to various factors, genetic and epigenetic (eg diet, pollutants, radiation). The modern research community suggests that intestinal dysbiosis, i.e the disturbance of the normal composition of the intestinal microbiome, is involved in the development of the neoplastic process. The aim of this study was to evaluate the association of the intestinal microbiome with the development of carcinogenesis in the large intestine and in response to anti-cancer therapies, aiming at possible findings that will have a positive impact on optimizing oncological therapies, and finding possible clinical biomarkers, useful for early detection and diagnosis of colon cancer. Existing studies on individual bacteria and a set of bacterial communities with oncogenic potential are reviewed. Also, the effect of microorganisms, as well as various dietary patterns and dietary interventions (probiotics, prebiotics, symbiotics) are evaluated, as well as, the effectiveness of existing anti-cancer therapies and their accompanying symptoms. Extensive research for different types of studies in the PubMed / MEDLINE database over the last decade, has been done. Overall, studies of intestinal dysbiosis as a risk factor for the development of carcinogenesis reveal various mechanisms, without one of them being superior to the other. An important feature was the heterogeneity, in terms of the methodology of the studies, such as a) type of interventions, b) confounding factors, c) duration of follow-up. In conclusion, several studies have shown that the abundance of specific species of bacteria predisposes to an increased risk of intestinal oncogenesis, each with a different mechanism of action. Some researchers did not accept this idea and thus, they argued that the bacterial communities as a whole, in the context of intestinal dysbiosis, are those that have a strong oncogenic dynamic and not individual bacteria. Both views can be equally influential in drawing a generally accepted conclusion. In the present dissertation, the effect of the intestinal microbiome in response to the contemporary anti-cancer therapies was also studied. Intestinal dysbiosis appears to play an important role in the response to chemotherapy, immunotherapy, and surgery, as well as being a potential condition for increasing the toxicity / adverse effects of these treatments. In addition, the role of diet in the formation of the intestinal microbiome and consequently in the risk of intestinal carcinogenesis was investigated, both individually with regard to macronutrients such as fat, food groups (eg meat), and as a whole dietary pattern for example western type, mediterranean type diet. According to peer research literature, it seems that the potential ability of pro-, prebiotic and symbiotic in order to inhibit oncogenesis or reduce the toxicity associated with anticancer therapies, have been evaluated. Moreover, a small number of studies have evaluated their potential to enhance therapeutic efficiency. Therefore, the method of targeting the intestinal microbiome seems to be very promising in terms of increasing the effectiveness of anti-cancer therapies and reducing their toxicity. However, it has not yet been well-documented and stated, due to the fact that the research community, has largely completed preclinical studies in animal models with ectopic tumors that have undergone immunoprocessing procedures prior to transfer to the new host. These models do not adequately reflect the ever-changing interactions between the immune system and the tumor during cancer elimination processes, in the equilibrium and escape stages. New insights in the underlying molecular mechanisms, humanized animal models or models of spontaneous oncogenesis will probably be needed.
Keywords:
Colorectal cancer, Gut microbiome, Gut dysbiosis, Anticancer therapies, Nutrition, Metabolic / Oncogenic pathways