Abstract
Biofilms enhance production of N1,N12-diacetylspermine and other polyamines in colon tumors.
Major finding: Biofilms enhance production of N1,N12-diacetylspermine and other polyamines in colon tumors.
Concept: Polyamines are metabolites that have been implicated in tumor cell proliferation and survival.
Impact: Biofilms may increase colon cancer risk by inducing specific changes to the colonic mucosal metabolome.
Bacteria that adhere to the colonic epithelium can aggregate to form structures known as biofilms that can disrupt the normal mucosal barrier of the colon. Biofilm-induced inflammation and changes in tissue homeostasis have been implicated in nonmalignant diseases such as inflammatory bowel disease, and recent evidence suggests that the presence of biofilms in the colon may be associated with increased risk of colon cancer. Hypothesizing that biofilms might induce metabolic changes that could promote colon tumorigenesis, Johnson, Dejea, and colleagues performed mass spectrometry–based analyses including untargeted metabolomics, nanostructure imaging mass spectrometry (NIMS), and global isotope metabolomic experiments. The analyses of two independent groups of colon cancer samples and matched normal tissues revealed that polyamine metabolites, particularly N1,N12-diacetylspermine, were specifically and significantly elevated in colon cancer samples compared with normal colon tissue. Levels of N1,N12-diacetylspermine and other polyamines were also significantly higher in biofilm-positive cancers compared with biofilm-negative cancers, indicating that polyamine production is elevated in colon cancers and is enhanced further by the presence of biofilms. This was validated by NIMS which revealed the localization of polyamine metabolites in situ at the mucosal edge of tumor tissue. Expression of polyamine metabolizing enzymes was similar in biofilm-positive and biofilm-negative colonic epithelium, indicating that the changes in metabolite levels are driven by the mucosa-associated microbial community and not the host. Consistent with this possibility, polyamine levels were decreased in patients who were treated with oral antibiotics prior to surgery compared with those who were not. Because polyamine metabolism is associated with inflammation and known to support cell proliferation, these findings raise the possibility that the presence of biofilms in the colonic mucosa provides a supportive environment for tumor growth by inducing specific metabolic changes and suggest that biofilm interactions within the tumor microenvironment may be a therapeutic target.