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Integrated in vitro and in silico Modelling Delineates the Molecular Effects of a Symbiotic Regimen on Colorectal Cancer-Derived Cells

53 Pages Posted: 20 Nov 2018 Publication Status: Review Complete

See all articles by Kacy Greenhalgh

Kacy Greenhalgh

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

Javier Ramiro-Garcia

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

Almut Heinken

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

Pit Ullmann

Universite du Luxembourg, Faculty of Science, Technology and Communication (FSTC), Life Sciences Research Unit

Tamara Bintener

Universite du Luxembourg, Faculty of Science, Technology and Communication (FSTC), Life Sciences Research Unit

Maria Pires Pacheco

Universite du Luxembourg, Faculty of Science, Technology and Communication (FSTC), Life Sciences Research Unit

Joanna Baginska

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

Pranjul Shah

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

Audrey Frachet

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

Rashi Halder

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

Joëlle V. Fritz

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine; Centre Hospitalier Luxembourg

Thomas Sauter

Universite du Luxembourg, Faculty of Science, Technology and Communication (FSTC), Life Sciences Research Unit

Ines Thiele

Universite du Luxembourg, Luxembourg Centre for Systems Biomedicine

Serge Haan

Universite du Luxembourg, Faculty of Science, Technology and Communication (FSTC), Life Sciences Research Unit

Elisabeth Letellier

Universite du Luxembourg, Faculty of Science, Technology and Communication (FSTC), Life Sciences Research Unit

Paul Wilmes

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

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Abstract

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.

Suggested Citation

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.

Kacy Greenhalgh

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine ( email )

2 Avenue de l'Université
Esch-sur-Alzette
Luxembourg

Javier Ramiro-Garcia

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

2 Avenue de l'Université
Esch-sur-Alzette
Luxembourg

Almut Heinken

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

2 Avenue de l'Université
Esch-sur-Alzette
Luxembourg

Pit Ullmann

Universite du Luxembourg, Faculty of Science, Technology and Communication (FSTC), Life Sciences Research Unit

Belvaux
Luxembourg
Luxembourg

Tamara Bintener

Universite du Luxembourg, Faculty of Science, Technology and Communication (FSTC), Life Sciences Research Unit

Belvaux
Luxembourg
Luxembourg

Maria Pires Pacheco

Universite du Luxembourg, Faculty of Science, Technology and Communication (FSTC), Life Sciences Research Unit

Belvaux
Luxembourg
Luxembourg

Joanna Baginska

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

2 Avenue de l'Université
Esch-sur-Alzette
Luxembourg

Pranjul Shah

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

2 Avenue de l'Université
Esch-sur-Alzette
Luxembourg

Audrey Frachet

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

2 Avenue de l'Université
Esch-sur-Alzette
Luxembourg

Rashi Halder

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

2 Avenue de l'Université
Esch-sur-Alzette
Luxembourg

Joëlle V. Fritz

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine

2 Avenue de l'Université
Esch-sur-Alzette
Luxembourg

Centre Hospitalier Luxembourg

Luxembourg
Luxembourg

Thomas Sauter

Universite du Luxembourg, Faculty of Science, Technology and Communication (FSTC), Life Sciences Research Unit

Belvaux
Luxembourg
Luxembourg

Ines Thiele

Universite du Luxembourg, Luxembourg Centre for Systems Biomedicine ( email )

2 Avenue de l'Université
Esch-sur-Alzette
Luxembourg

Serge Haan

Universite du Luxembourg, Faculty of Science, Technology and Communication (FSTC), Life Sciences Research Unit

Belvaux
Luxembourg
Luxembourg

Elisabeth Letellier

Universite du Luxembourg, Faculty of Science, Technology and Communication (FSTC), Life Sciences Research Unit

Belvaux
Luxembourg
Luxembourg

Paul Wilmes (Contact Author)

Universite du Luxembourg - Luxembourg Centre for Systems Biomedicine ( email )

2 Avenue de l'Université
Esch-sur-Alzette
Luxembourg

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