The gut microbiome in colorectal adenomas

Abstract

How the gut microbiome is altered in patients with bowel polyps and contributes to polyp progression is poorly understood. This thesis investigated the microbiome in early bowel neoplasia. 16S rRNA gene amplicon sequencing, Pacbio long-read sequencing, univariate and multivariate analyses were used to profile differences in microbiome compositions between participants with bowel polyps and those without, and participants with high-risk versus low-risk polyps. Quantitative PCR of genes in the bacterial butyrate production pathway was used to compare differences in butyrate potential in participants with bowel polyps and those without. Participants with early bowel polyps and those without showed minimal differences in alpha or beta diversity. However, these groups showed differentially abundant bacteria, the proximal and distal polyp environments differed in relevant bacteria, and furthermore, different types of polyps showed different microbial environments. Similarly, participants with high-risk compared to low-risk polyp progression to CRC showed differential abundance in microbiota and different immune density profiles, and these patterns differed between the proximal and distal colon, suggesting that proximal and distal polyps inhabit different environments. Finally, participants with polyps showed lower Faecalibacterium prausnitzii but gene levels, but higher Anaerostipes and Eubacterium but gene levels, compared to healthy controls. This thesis has identified microbial candidates in the colonic mucosa and oral cavity that are associated with early bowel neoplasm, which require further validation, particularly in how they may interact with other factors in the polyp environment. These results have potential for improving disease risk assessment and understanding how microbes contribute to bowel cancer development.