Show simple item record

dc.contributor.authorGreenhalgh, Kacy
dc.contributor.authorRamiro-Garcia, Javier
dc.contributor.authorHeinken, Almut
dc.contributor.authorUllmann, Pit
dc.contributor.authorBintener, Tamara
dc.contributor.authorPires Pacheco, Maria
dc.contributor.authorBaginska, Joanna
dc.contributor.authorShah, Pranjul
dc.contributor.authorFrachet, Audrey
dc.contributor.authorHalder, Rashi
dc.contributor.authorFritz, Joëlle V.
dc.contributor.authorSauter, Thomas
dc.contributor.authorThiele, Ines
dc.contributor.authorHaan, Serge
dc.contributor.authorLetellier, Elisabeth
dc.contributor.authorWilmes, Paul
dc.identifier.citationGreenhalgh, Kacy, Ramiro-Garcia, Javier, Heinken, Almut, Ullmann, Pit, Bintener, Tamara, Pires Pacheco, Maria, Baginska, Joanna, Shah, Pranjul, Frachet, Audrey, Halder, Rashi, Fritz, Joëlle V. Sauter, Thomas, Thiele, Ines, Haan, Serge, Letellier, Elisabeth, Wilmes, Paul. (2019). Integrated In Vitro and In Silico Modeling Delineates the Molecular Effects of a Synbiotic Regimen on Colorectal-Cancer-Derived Cells. Cell Reports, 27(5), 1621-1632. doi:10.1016/j.celrep.2019.04.001en_IE
dc.description.abstractBy 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-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 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 modeling for rationally formulating synbiotics-based treatments in the future.en_IE
dc.description.sponsorshipThe authors would like to thank Dr. Christian Jäger at the LCSB Metabolomics Platform for helpful discussions and metabolite quantification, and Martine Schmitz for RT-PCR validation analysis. We thank the contributing surgeons from the Centre Hospitalier Emile Mayrisch in Esch-sur-Alzette and the nurses of the Clinical and Epidemiological Investigation Center of the Luxembourg Institute of Health for collecting samples for research purposes. The authors wish to thank Frutarom for providing the SoyLife prebiotic. K.G. was supported by an AFR PhD fellowship from the Luxembourg National Research Fund (FNR; AFR/PHD/9964547 ). This work was supported by a Luxembourg Personalised Medicine Consortium pump-prime grant (PerPreProBioCRC) and a proof-of-concept grant ( PoC/15/11014639 ) from the FNR , awarded to P.W. The project was also supported through an internal research project grant (IRP; MiDiCa) from the University of Luxembourg to S.H. and P.W., and two CORE Junior grants ( C14/BM/8066232 and C16/BM/11282028 ) awarded to J.F. and E.L., respectively. This work was further supported by an ATTRACT Programme grant ( FNR/A12/01 ) awarded to I.T., a European Research Council (ERC) grant under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 757922 ) awarded to I.T., and an FNR grant ( PRIDE15/10675146/CANBIO ) to T.B.en_IE
dc.publisherCell Pressen_IE
dc.relation.ispartofCell Reportsen
dc.subjectgut microbiomeen_IE
dc.subjectcolorectal canceren_IE
dc.subjectnutritional therapyen_IE
dc.titleIntegrated in vitro and in silico modelling delineates the molecular effects of a synbiotic regimen on colorectal cancer-derived cellsen_IE
dc.contributor.funderFonds National de la Recherche Luxembourgen_IE
dc.contributor.funderHorizon 2020en_IE
dc.local.contactInes Thiele. Email:
dcterms.projectinfo:eu-repo/grantAgreement/EC/H2020::ERC::ERC-STG/757922/EU/Predicting the effects of gut microbiota and diet on an individual’s drug response and safety/BugTheDrugen_IE

Files in this item

Attribution-NonCommercial-NoDerivs 3.0 Ireland
This item is available under the Attribution-NonCommercial-NoDerivs 3.0 Ireland. No item may be reproduced for commercial purposes. Please refer to the publisher's URL where this is made available, or to notes contained in the item itself. Other terms may apply.

The following license files are associated with this item:


This item appears in the following Collection(s)

Show simple item record