The role of metabolites in colon cancer

Colon Cancer Pathways Diagram

The clinical outcome for patients with colon cancer has been improving over the past 30 years due to implementation of screening and efficient therapeutics. However, colon cancers that present on the right versus the left side of the colon have significantly worse prognosis for the patient. A recent discovery revealed that right-sided colon cancers (RCCs) harbor mucosal bacterial biofilms, whereas left-sided colon cancers (LCC) are predominantly devoid of biofilms. These biofilms are associated with increased cellular proliferation and inflammation even in normal colon tissues. Using mass spectrometry-based metabolomics, we investigated the metabolism of colon cancers with and without biofilms, and observed a correlation between increased N1, N12-diacetylspermine production and biofilm presence on RCCs. Using antibiotic treatment, IHC, and stable isotope-assisted metabolomics we showed that N1, N12-diacetylspermine is an end product of polyamine metabolism produced by bacterial biofilms. We thus hypothesized that microbiota use host-derived polyamines to form biofilms. It is still not known why biofilms only form only on RCC, but it could be due to other factors such as diet and genetic predisposition. 

Therefore, the aims of my lab are to examine the influence of these factors in LCC and RCC pathogenicity by investigating the roles of dietary metabolites, microbial communities and genetic predisposition.