Elucidating the mechanisms of anastomotic leakage: a new point of view

After surgical resection of a part of the colon an anastomosis is made to restore the continuity of the colon. Unfortunately, these anastomoses are often complicated by leakage. This thesis embarks on the quest to elucidate the mechanisms behind anastomotic leakage (AL). New techniques are used to study a long-ignored factor in AL: the intestinal microbiota. We demonstrate that the bacterial composition during the construction of the anastomosis plays a role in the subsequent development of anastomotic leakage. The lack of diversity in the microbial composition is associated with AL. Furthermore, the virulence factors (pathogenic molecules) of bacteria and other micro-organisms play an important role in the development of AL and the associated subsequent tumour recurrence. These virulence factors are a high expression of the collagen degrading GelE gene and the ability to activate the collagen degrading MMP9, together called the “leakage phenotype”. The Western diet causes a change in and reduction of the microbial diversity and a presence of micro-organisms with the “leakage phenotype”. Lastly, the expression of genes in the colon plays a role in AL, with a reduced expression of genes involved in the immune response, angiogenesis and collagen crosslinking. To conclude: the intestinal microbiota, partly influenced by the Western diet, and the colonic gene expression are important factors in the development of AL. In the nearby future, the results from this thesis can be used for therapeutic or preventive measures to prevent anastomotic leakage, partly focused on the manipulation of the intestinal microbiota.