Background

Differences in the colonic microbiome of obese and non-obese patients have been postulated to modify the risk of developing colorectal cancer, however it is unclear if differences persist after cancer formation and if these are localised to the normal mucosa, tumour mucosa or both.

Methods

Patients undergoing operative colorectal resection for colorectal cancer were recruited at one London hospital. Tumour and paired normal mucosa were sampled ex vivo from the surgical specimen and underwent DNA extraction. The V1-V2 regions of the bacterial 16S rRNA gene were amplified and sequenced. Analysis was conducted using an in-house pipeline to compare the tumour and normal mucosal microbiome of obese and non-obese patients (obesity defined as BMI greater than 30kg/m2).

Results

350 mucosal samples (169 adenocarcinoma, 181 normal mucosa) were sequenced from 197 patients with a mean age of 70.9. The median BMI was 26.8 (range 15.1-49.1) with 54 patients diagnosed as obese. There was no difference in the alpha diversity of microbial species on the normal mucosa of obese compared to non-obese patients (Shannon diversity index 5.00 vs 5.03 respectively, p=0.79), however there was significantly reduced alpha diversity on the tumour mucosa of non-obese patients compared to obese patients (4.61 vs 4.97 respectively, p=0.03). Propensity matched analysis based on age, gender and type of procedure demonstrated that the tumour mucosa of obese patients had significantly lower abundance of fusobacterium compared to non-obese tumour mucosa (p=0.02). Paired normal mucosa showed no differential abundance between obese and non-obese patients.

Conclusions

The microbiome of colorectal tumour mucosa has significant differences comparing obese and non-obese patients, which are not replicated when looking at the respective paired normal mucosa. This implies that potential microbial drivers of carcinogenesis are not different between obese and non-obese patients, however the tumour microenvironment is ecologically distinct.