| Autor: |
Maria Irene Pires Pacheco, Audrey Frachet, Tamara Jean Rita Bintener, Joëlle V. Fritz, Serge Haan, Pranjul Shah, Thomas Sauter, Elisabeth Letellier, Javier Ramiro-Garcia, Kacy Greenhalgh, Rashi Halder, Pit Ullmann, Paul Wilmes, Joanna Baginska, Almut Heinken, Ines Thiele |
| Rok vydání: |
2018 |
| Předmět: |
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| Zdroj: |
SSRN Electronic Journal. |
| ISSN: |
1556-5068 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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