By modulating the human gut microbiome, prebiotics and probiotics (combinations of which are called synbiotics) may be used to treat diseases such as colorectal cancer (CRC). Methodological limitations have prevented determining the potential combinatorial mechanisms of action of such regimens. We expanded our HuMiX gut-ona- chip model to co-culture CRC-derived epithelial cells with a model probiotic under a simulated prebiotic regimen, and integrated the multi-omic results with in silico metabolic modelling. In contrast to individual prebiotic or probiotic treatments, the synbiotic regimen caused downregulation of genes involved in procarcinogenic pathways and drug resistance, and reduced levels of the oncometabolite lactate. Distinct ratios of organic and short-chain fatty acids were produced during the simulated regimens. Treatment of primary CRC-derived cells with a molecular cocktail reflecting the synbiotic regimen attenuated self-renewal capacity. Our integrated approach demonstrates the potential of modelling for rationally formulating synbiotics-based treatments in the future.
Greenhalgh, Kacy and Ramiro-Garcia, Javier and Heinken, Almut and Ullmann, Pit and Bintener, Tamara and Pacheco, Maria Pires and Baginska, Joanna and Shah, Pranjul and Frachet, Audrey and Halder, Rashi and Fritz, Joëlle V. and Sauter, Thomas and Thiele, Ines and Haan, Serge and Letellier, Elisabeth and Wilmes, Paul, Integrated
in vitro and
in silico Modelling Delineates the Molecular Effects of a Symbiotic Regimen on Colorectal Cancer-Derived Cells (November 20, 2018). Available at SSRN: https://ssrn.com/abstract=3287784 or http://dx.doi.org/10.2139/ssrn.3287784
This version of the paper has not been formally peer reviewed.
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