Exploring the role of the microbiome, gut barrier dysfunction, host genetics, and metabolic interactions in the development of colorectal cancer

Background: Accumulating research suggests that a disturbance in the gut microbiome can influence development of colorectal neoplasia from early lesions to tumours (1).

Hypothesis: Gut microbiome involvement in colorectal carcinogenesis may occur through inflammatory-induced weakening of the protective gut mucosal barrier by obesity, dietary/lifestyle, and microbiome metabolic factors that lead to exposure of the gut epithelium to pathogenic bacteria and their toxins (2-4).

Objective: To apply circulating (liquid biopsy) measures of gut barrier dysfunction and bacterial translocation into the circulation as biomarkers of colorectal carcinogenesis and disease progression. Blood-based detection of bacteria and gut-barrier health may allow novel screening strategies for CRC cancer prevention, diagnosis, and management.

Methodology: Measures of gut barrier dysfunction will be assessed by protein ELISA assays, while bacterial translocation and metabolic activity will be ascertained by bacterial antigen immunotyping, plasma metabolomics, and circulating bacterial DNA sequencing. The contribution of host genetics related to immune/microbiome and microbial metabolite interactions will be assessed using existing GWAS data. This will be conducted in patient case-control cohorts of colorectal adenomas and cancer, available in UCD and through ColoMARK partners. Additionally, the project will include data analysis integration with the metabolomics data, together with detailed anthropometric and lifestyle data, from 1,120 matched case-control pairs nested within the EPIC cohort in DC2. Analytic approaches will include multivariable logistic regression and mediation analyses. Thus, this PhD will involve laboratory assays such as ELISA assays, qPCR, and metagenomic sequencing, but there will be a major focus on biostatistical and bioinformatic approaches. Together, this will help shed light on the involvement of microbial translocation and microbially derived metabolic perturbations on adenoma progression and CRC development.

For further details see https://www.ucd.ie/sbbs/research/researchvacancies/

This project has received funding from the European Union´s Horizon Europe Research and Innovation Programme under the Marie Skłodowska-Curie Doctoral Network grant agreement. This PhD position is available in University College Dublin (UCD), Ireland within an MSCA Doctoral Network, ColoMARK, that aims to train a next-generation of skilled researchers in the field of liquid biopsy biomarkers in CRC.