计算机模拟基因表达,体外共培养+计算机模拟，分析合生制剂对结直肠癌细胞的影响...

体外实验与计算机模拟分析合生制剂对结直肠癌细胞的分子影响

10.1016/j.celrep.2019.04.001

2019-04-30, Article

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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-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.

First Authors:

Kacy Greenhalgh

Correspondence Authors:

Paul Wilmes

All Authors:

Kacy Greenhalgh,Javier Ramiro-Garcia,Almut Heinken,Pit Ullmann,Tamara Bintener,Maria Pires Pacheco,Joanna Baginska,Pranjul Shah,Audrey Frachet,Rashi Halder,Joëlle V Fritz,Thomas Sauter,Ines Thiele,Serge Haan,Elisabeth Letellier,Paul Wilmes