Article (Scientific journals)
Integrated In Vitro and In Silico Modeling Delineates the Molecular Effects of a Synbiotic Regimen on Colorectal-Cancer-Derived Cells
GREENHALGH, Kacy; RAMIRO GARCIA, Javier; Heinken et al.
2019In Cell Reports, 27, p. 1621–1632
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Abstract :
[en] 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 combina- torial mechanisms of action of such regimens. We expanded our HuMiX gut-on-a-chip model to co-culture CRC-derived epithelial cells with a model probiotic under a simulated prebiotic regimen, and we integrated the multi-omic results with in silico metabolic modeling. In contrast to individual prebi- otic or probiotic treatments, the synbiotic regimen caused downregulation of genes involved in procarci- nogenic 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 ca- pacity. Our integrated approach demonstrates the potential of modeling for rationally formulating synbi- otics-based treatments in the future.
Research center :
Luxembourg Centre for Systems Biomedicine (LCSB)
Disciplines :
Life sciences: Multidisciplinary, general & others
Author, co-author :
GREENHALGH, Kacy ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
RAMIRO GARCIA, Javier ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Heinken
Ullmann, Pit
BINTENER, Tamara Jean Rita ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
PACHECO, Maria ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Baginska, joanna
SHAH, Pranjul ;  University of Luxembourg > Rectorate > Academic Affairs
FRACHET BOUR, Audrey ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
HALDER, Rashi ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
FRITZ, Joëlle ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
SAUTER, Thomas ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
Thiele, Ines;  National University of Galway
HAAN, Serge ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
LETELLIER, Elisabeth ;  University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit
WILMES, Paul ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
More authors (6 more) Less
External co-authors :
no
Language :
English
Title :
Integrated In Vitro and In Silico Modeling Delineates the Molecular Effects of a Synbiotic Regimen on Colorectal-Cancer-Derived Cells
Publication date :
30 April 2019
Journal title :
Cell Reports
ISSN :
2211-1247
Publisher :
Elsevier, Amsterdam, Netherlands
Volume :
27
Pages :
1621–1632
Peer reviewed :
Peer Reviewed verified by ORBi
FnR Project :
FNR9964547 - A Study Of The Molecular Mechanisms Underlying The Response Of Human Colorectal Adenocarcinoma Enterocytes To Prebiotics/Probiotics, 2015 (01/03/2015-31/01/2019) - Kacy Greenhalgh
Funders :
FNR - Fonds National de la Recherche [LU]
Available on ORBilu :
since 21 May 2019

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