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Complexity science for immune fitness

Specialised nutrition and nutritional supplements aim at improving the “immune fitness” of both patients and healthy people. The goal is this interdisciplinary project is to quantify the effect of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in-vitro, in-vivo and in-silico using a complex systems approach. We will develop a computational framework to study the complex dynamics of the resolution of systemic and chronic inflammation. This framework will help to identify the optimal nutritional plan based on n-3 PUFAs to maximise the immune fitness and provide a faster resolution of inflammation.

The World Health Organization (WHO) has recently acknowledged the central role of immune fitness in the management of both acute and chronic diseases. Most definitions of immune fitness mention the ability of the immune system to respond appropriately, adaptively and in a responsive manner to a challenge. However, we currently lack metrics to assess these mechanisms and thus any quantitative evaluation of the immune fitness of a person is precluded. Computational models can provide a way forward to unravel the intricacies of immune fitness and to define such quantitative metrics.

The role of n-3 PUFAs as precursors to specialised pro-resolving lipid mediators with dual anti-inflammatory and pro-resolving bioactivity is well documented. However, a clear quantitative understanding of their effect in mediating inflammatory processes is not yet available and clinical trials report contradictory results. Consequently, the effectiveness of n-3 PUFAs as a dietary supplement to enhance “immune fitness” in terms of resolution of systemic and chronic inflammation cannot be clearly determined.

The UvA Institute for Advanced Study (IAS) in collaboration with the Tytgat Institute for Liver and Intestinal Research (AMC) and the Utrecht Institute for Pharmaceutical Science (UU) is developing an integrated framework based on complexity thinking. This generalised model of human innate immune response will be used to provide a quantitative definition of “immune fitness” and to quantitatively evaluate the resolution of inflammation in various diseases (such as type-2 diabetes, inflammatory bowel syndrome and systemic inflammation after invasive surgery) as a function of a diet based on n-3 PUFAs or other nutritional supplements.