Research project
24 | monthsSIL_FOOD

Use of in silico models to tackle malnutrition

Related toSpoke 06

Principal investigators
Emilio Benfenati

Other partecipantsGianluca Selvestrel, Sofia Ghironi
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Task involved

Task 6.2.2.

Development and application of in vitro, in vivo and in silico experimental models for the understanding of the mechanism of action in counteracting malnutrition of new sustainable bioactive molecules from different matrices (in connection with Spoke 2, 3 and 4).

Project deliverables

D6.2.2.2.

Identification of at least 7 sustainable bioactive molecules: a) 3 proven to directly impact nutritional status b) 2 proven to impact gut satiety hormones release c) 2 proven to reduce skeletal muscle mass decline in elderly populations with specific pathologies and/or nutritional impairments (M24)

State of the art

The evaluation of the effects of food components and the balance between adverse and beneficial contributions, is difficult. Nowadays only partial elements are available. More and more studies investigate the adverse effects of substances in food and potential beneficial effects. Adversities are evaluated through methods which are not always standardized and this makes difficult to gain a sound overview of the critical impact of substances. In silico models are based on collections of experimental data produced according to well-defined procedures, to minimize the noise of the input data. Thus, the paucity of data limits the development of in silico models. On the other side, in silico models can be developed codifying relevant mechanisms, and this helps to explore adverse effect, associated to specified pathways, integrating toxicodynamic and toxicokinetics, and ideally combining adverse effects and potential beneficial effects.

Operation plan

In silico models will be developed integrating three aspects: 

  • the statistical-based modelling strategy, based on multiple substances; 
  • the read-across approach, based on the similarity of substances with experimental values; 
  • and the theoretical information, as mechanism of actions (MoA) on malnutrition status (such as obesity condition). 

These MoA will be investigated, also based on the information provided within the project in the other tasks and will be defined as steps composing the overall process, with a reference to what is called adverse outcome pathway (AOP), as a conceptual framework. In this way, the in silico models will be in a dialogue with the other experimental methods, within the same WP. The properties addressed will be both the adverse and the beneficial ones. This will be useful to identify directions of future foods, both identifying ingredients to be avoided, but also to propose novel foods ameliorating the nutritional and health status of ill patients.

Expected results

In silico models will integrate different approaches. The models will produce a prediction on the expected beneficial and adverse effects on the different kinds of malnutrition; they will also allow the identification of similar substances with their experimental values, and the indication of the mechanism associated to the effect, represented by specific molecular moieties.