Changes in the composition of the gastrointestinal microbiota are associated with the development of colorectal cancer, and prebiotics have been proposed as a tool to modulate these changes and prevent disease. However, there is a lack of physiologically relevant coculture platforms to evaluate the effect of prebiotics on colonocytes within the complex tumor microenvironment. To address this need, we developed a microfluidic device to coculture a diverse gastrointestinal microbiota with tumor-derived colonocytes within an anoxic, three-dimensional microenvironment typical of solid tumors. We demonstrate the effect of this culture microenvironment on the expression of cancer-related genes in colonocytes, as well as the possibility of sustaining bacterial diversity and colonocyte viability during coculture enabled by microfluidic technology. We employ this platform to evaluate the effect of prebiotic compounds on microbiota composition and the subsequent impact on colonocyte viability and gene expression. Our results exemplify the potential of complex coculture models to improve our understanding of the role of prebiotics on gastrointestinal physiology and to design prebiotic interventions as microbiota-mediated disease prevention tools.

Investigating prebiotics in a microfluidic model of colorectal cancer

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ACS Fall 2022

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