Abstract
Colon cancer induces a state of mucosal dysbiosis with associated niche specific changes in the gut microbiota. However, the key metabolic functions of these bacteria remain unclear. We performed a prospective observational study in patients undergoing elective surgery for colon cancer without mechanical bowel preparation (n = 18). Using 16 S rRNA gene sequencing we demonstrated that microbiota ecology appears to be cancer stage-specific and strongly associated with histological features of poor prognosis. Fusobacteria (p < 0.007) and ε- Proteobacteria (p < 0.01) were enriched on tumour when compared to adjacent normal mucosal tissue, and fusobacteria and β-Proteobacteria levels increased with advancing cancer stage (p = 0.014 and 0.002 respecitvely). Metabonomic analysis using 1H Magic Angle Spinning Nuclear Magnetic Resonsance (MAS-NMR) spectroscopy, demonstrated increased abundance of taurine, isoglutamine, choline, lactate, phenylalanine and tyrosine and decreased levels of lipids and triglycerides in tumour relative to adjacent healthy tissue. Network analysis revealed that bacteria associated with poor prognostic features were not responsible for the modification of the cancer mucosal metabonome. Thus the colon cancer mucosal microbiome evolves with cancer stage to meet the demands of cancer metabolism. Passenger microbiota may play a role in the maintenance of cancer mucosal metabolic homeostasis but these metabolic functions may not be stage specific.
Highlights
Sporadic colorectal cancer (CRC) is the third commonest cause of cancer-related death worldwide and its global incidence is increasing[1]
Five patients had extramural vascular invasion (EMVI), which is a histological feature of poor prognosis, and two of these were found to express the KRAS mutation
The oral Gram negative bacterium Fusobacterium nucleatum has been strongly associated with adenomas of the colon and rectum[12, 15, 16, 25]
Summary
Sporadic colorectal cancer (CRC) is the third commonest cause of cancer-related death worldwide and its global incidence is increasing[1]. Important weaknesses of many existing studies examining the colonic microbiota in cancer aetiology are the employment of heterogeneous sampling approaches, the limited oncological phenotyping data presented and the variable use of mechanical bowel preparation[8,9,10,11,12,13,14,15,16] This heterogeneity is critical as such variation is likely to influence the ecological characteristics of the microbiota: for example recent data from patients undergoing lower gastrointestinal tract endoscopy have identified short-term changes in the colonic microbiome caused by use of mechanical bowel preparation[17, 18]
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