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
创作:szx 审核:szx 2019年05月10日
  • 基于微流控的共培养系统HuMiX,结合多组学分析及计算机模拟结果,研究结直肠癌细胞、鼠李糖乳杆菌GG株(LGG)及膳食纤维间的互作;
  • 与单独的益生菌/元处理相比,合生制剂下调促进癌变及耐药性相关通路的基因表达,并可降低促癌变代谢产物——乳酸盐的水平;
  • LGG产生的有机酸/短链脂肪酸比例受到饮食影响,有机酸与短链脂肪酸的不同组合对结直肠癌细胞有着不同影响;
  • 合生制剂产生的小分子组合,可抑制结直肠癌细胞的自我更新能力。
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szx
《Cell Reports》上发表的一项最新研究,结合了体外共培养系统及计算机模拟方法,分析了合生制剂(鼠李糖乳杆菌GG株+膳食纤维)对结直肠癌细胞的影响。
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Cell Reports [IF:8.109]

Integrated In Vitro and In Silico Modeling Delineates the Molecular Effects of a Synbiotic Regimen on Colorectal-Cancer-Derived Cells

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

Abstract & Authors:展开

Abstract:收起
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

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