A new study from King’s College London and the Francis Crick Institute may help explain the link between diet and disease. Researchers in the study built a modelling tool to predict the effects of different diets on cancerous vs healthy cells in mice.
As part of the study, published in iScience, a research team from the Centre for Host-Microbiome Interactions at King’s College London first created a comprehensive map of all metabolic pathways in the mouse. Metabolism is the set of processes that allow an organism to use nutrients from its environment in order to function. Cancer cells, like other diseased cells, change their metabolism to support survival and growth.
The Crick team then gathered experimental data to put into the model by measuring the levels of gene expression in liver and liver tumours from mice that had been fed either ‘healthy’ diets or ‘unhealthy’ diets, rich in fats and sugars. The results showed differences in metabolism between healthy and cancerous cells were highest in the context of an unhealthy diet, suggesting that tumours are able to better exploit unhealthy diets to promote survival and growth.
The potential applications of this work are far reaching. We can now see which changes in diet actually impact cell metabolism, and which have very little effect because the cells are already programmed to draw missing nutrients from their surroundings.– Dr Frederick Clasen, first author and Research associate at King's College London
Speaking on the study, Patricia Nunes, contributing author and Senior Laboratory Research Scientist at the Crick said, ‘By using experimental data from the lab, the model allows us to start understanding the complex metabolic changes that happen in tissues due to specific nutrients in the diet.’
The study modelled the effects of a change in dietary components - from healthy to unhealthy, and unhealthy to healthy - in various combinations. Although some cancer-specific metabolic functions persisted on healthy diets, researchers found they could also reverse many of them, but only when both fats and carbohydrates were limited.
To further increase the accuracy of our model’s predictions, we are now generating more sophisticated models of metabolism, that take into account how different organs exchange metabolites, and how bacteria in the gut influence what nutrients are available to tissues.– Dr Saeed Shoaie, group leader of Translational Systems Biology at King's College London and contributing author
The authors hope the approach from their study could be used to help guide dietary changes that complement treatments for different diseases. Dimitrios Anastasiou, head of the Crick’s Cancer Metabolism Laboratory, concluded, ‘We know that poor diet wreaks havoc in our body’s metabolism. It can cause obesity and promote liver disease, which, in turn, can progress to liver cancer. We want to understand which nutrients in our diets, and in what combinations, drive these detrimental outcomes… The most effective use of this understanding will be in preventing more disease by helping us select the foods we eat.’
Clasen, F., Nunes, P.M., Bidkhori, G., Bah, N., Boeing, S., Shoaie, S., Anastasiou, D. (2023) Systematic diet composition swap in a mouse genome-scale metabolic model reveals determinants of obesogenic diet metabolism in liver cancer, ISCIENCE (2023)
Doi: https:// doi.org/10.1016/j.isci.2023.106040.