Differences In Normal Mucosa And Colorectal Tumour Microbiota Between Right And Left Colon

IntroductionColorectal cancer (CRC) is categorised by colonic location of the primary tumour. Right-sided colon cancers (RCC) are found in the ascending and transverse colon. Whereas, left-sided colorectal cancers (LCC) are found in the descending colon, sigmoid colon and the rectum. The right and left colon have many distinctive developmental and physiological differences, which may explain the variations in outcomes, prognosis and response to therapy between RCC and LCC. In addition, the variability also observed in genetic mutations and oncogenic signalling pathways between RCC and LCC has led to stratifying CRC patients to right or left for treatment and clinical trials. However, the differences in mucosal adherent microbiota between the right and left colon and RCC and LCC has not been fully categorised.MethodsNormal and tumour biopsies were obtained post-surgery from 15 patients with RCC and 7 patients with LCC and were analysed for mucosal adherent gut microbiota using 16S rRNA profiling. Bacterial α-diversity was assed using the Shannon diversity index. All patients had either T3 or T4 stage tumours, had iron deficiency anaemia and were treated with intravenous ferric carboxymaltose prior to surgery.ResultsSpecies α-diversity in the right colon was significantly greater than the left colon (p=0.045). However, the species α-diversity between RCC and LCC showed no difference. To assess whether this was due to a decrease in RCC α-diversity or an increase in LCC α-diversity, we compared the right colon to the RCC and the left colon to the LCC. Species α-diversity was consistent between RCC and adjacent right colon, whereas, the LCC had significantly higher bacterial α-diversity than the adjacent left colon (p=0.015).ConclusionThese results suggest that under normal physiological conditions the right and left colon have different bacterial diversities. However, in CRC the tumour associated bacteria show similar diversities regardless of location. This may suggest that the LCC has acquired a mechanism to increase bacterial populations, potentially to support tumour growth. Ongoing work will determine the individual bacterial species associated with this increase in LCC α-diversity. The outcome is potentially beneficial when stratifying CRC patients, due to the development of probiotic therapies and biological drugs.