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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.date.accessioned2020-12-14T13:25:48Z
dc.date.available2020-12-14T13:25:48Z
dc.date.issued2019-04-30
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.identifier.issn2211-1247
dc.identifier.urihttp://hdl.handle.net/10379/16385
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.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherCell Pressen_IE
dc.relation.ispartofCell Reportsen
dc.subjectgut-on-a-chipen_IE
dc.subjectmodelingen_IE
dc.subjectgut microbiomeen_IE
dc.subjectprebioticen_IE
dc.subjectprobioticen_IE
dc.subjectsymbioticen_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.typeArticleen_IE
dc.date.updated2020-12-14T10:30:11Z
dc.identifier.doi10.1016/j.celrep.2019.04.001
dc.local.publishedsourcehttps://doi.org/10.1016/j.celrep.2019.04.001en_IE
dc.description.peer-reviewedpeer-reviewed
dc.contributor.funderFonds National de la Recherche Luxembourgen_IE
dc.contributor.funderHorizon 2020en_IE
dc.internal.rssid16935352
dc.local.contactInes Thiele. Email: ines.thiele@nuigalway.ie
dc.local.copyrightcheckedYes
dc.local.versionPUBLISHED
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
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