Fish-AI reached a fundamental milestone on its way toward an artificial intestine

The Fish-AI consortium successfully reached a crucial milestone of the project, bringing it one step closer to its final mission.

The consortium has completed the development of its artificial intestine prototype. This new platform combines the in vitro digestion of fish feed with a functional intestinal epithelium in a way that enables its prolonged exposure to the digested pellets for the study of how amino acids and other nutrients are absorbed through the intestinal wall.

Aquaculture is constantly growing due to the high demand for fish intended for human consumption. However, most of them are carnivorous and therefore fed using fish-derived products, obtained by processing small aquatic species. This generates a high environmental impact, compromising the sustainability of this food-producing sector. Therefore, the quest for novel feed ingredients that fit the concept of circular economy and have a smaller environmental footprint.

The combined and synergic efforts among Partners resulted in 4 publications in scientific journals!

The Consortium successfully designed and realized a hydrogel-based scaffold that can be processed in a 3D villi shape. This provides a mechanical support that maintains the physiological parameters of permeability and stiffness where rainbow trout intestinal cells can proliferate.

Schematic figure of the gelatin-based hydrogel construct development and its combination with RT-diMI cells. The image was created using Biorender.com.

In parallel, the team developed a procedure for extracting the bio-accessible fraction from feed pellets in a way that the resulting product can be easily added to the intestinal cells without damaging their functions. This enabled to quantify the absorption rate of single amino acids.

Fish-AI consortium set up the protocol to digest in vitro rainbow trout commercial diets in order to obtain a bio accessible fraction (BAF) suitable for cell culture. The image was created using Biorender.com.

The understanding that the scaffold has a profound influence on the capacity of the intestinal cell lines to fully differentiate in mature enterocytes, the intestinal cells that absorb the nutrients, has been a key moment. This led to the development of a cell-based organotypic platform formed by the supportive connective tissue combined with the functional intestinal epithelium.  The two together provide the best replica of the complex architecture of the intestinal wall and boost the epithelial cell differentiation.

UMIL team developed different in vitro intestinal platforms using the intestinal cell lines, recently isolated from Rainbow trout proximal and distal gut. These cell-based models reproduce morphologically and functionally the intestinal epithelium. The image was created using Biorender.com.

The last set of experiments demonstrated that the newly developed prototypes can be used for prolonged exposure to in vitro digested feed so that various functional parameters can be recoded. This enables the  development of a functional profile that can be applied to the ranking of different feed formulations.

The newly established cell-based intestinal platforms were combined to bio-accessible fraction to assess the suitability of the model to perform nutritional studies. The image was created using Biorender.com.

All partners are now working towards the next step of the project that consists in the direct comparison between in vivo and in vitro evaluation of a set of different diets with the aim of testing to which extent the Fish-AI prototype can provide reliable functional data that can support and partially substitute the in vivo feeding trials.

This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 828835.