Understanding the Role of the Microbiome in Deficient and Proficient Mismatch Repair Colorectal Cancers

Links between colorectal cancer (CRC) and the gut microbiome have been established, but the specific microbial species and their roles in carcinogenesis remain active areas of inquiry. Part of the mystery behind these links relates to the different methods of study that bias toward different signatures. In this webinar, Nicholas Chia will present work that elucidates the role of specific subtypes of CRC and discuss the implications of these findings for future research.

Chia and colleagues collected paired colon tumor and normal-adjacent tissue and mucosa samples from 83 individuals who underwent partial or total colectomies for CRC. Mismatch repair (MMR) status was determined in each tumor sample and classified as either deficient MMR (dMMR) or proficient MMR (pMMR) tumor subtypes. Samples underwent 16S rRNA gene sequencing and a subset of samples from 50 individuals were submitted for targeted metabolomic analysis to quantify amino acids and short-chain fatty acids. A PERMANOVA was used to identify the biological variables that explained variance within the microbial communities. dMMR and pMMR microbial communities were then analyzed separately using a generalized linear mixed-effects model that accounted for MMR status, sample location, intra-subject variability, and read depth.

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