Exploring the Gut-Liver Axis Using Organ-on-Chips and Liver Spheroids: A Path to Improving Liver Health
Objective
Addressing the Non-Alcoholic Fatty Liver Disease requires a comprehensive understanding of the intricate mutual interplay between the gastrointestinal tract and the liver. However, systematic and quantitative studies of the Gut-Liver Axis are quite limited due to a lack of reliable experimental models able to mimic human in vivo responses. We here show a novel multi-compartmental organ on chip (OO) platform for co-culturing intestinal and liver human tissues under fluid-dynamic conditions mimicking the physiological bloodstream.
Method
By employing the cutting-edge OOC technologies, we have developed an in vitro model of gut-liver axis where a human small intestinal epithelium is fluidically connected to HEPG2 liver cells, for investigating their crosstalk with and without the presence of bacteria in the gut lumen. Different treatments can be tested resembling the oral administration route; the hepatotoxicity is monitored over time through the sampling of culture media for LDH analysis and Albumin secretion. Moreover, the proper intestinal tissue integrity is analysis by measuring the trans-epithelial electrical resistance.
Results & Conclusions
We have already successfully demonstrated that this multi-organ configuration of OOCs allows the sampling of culture media from different physiological niches, with an improved reliability in drug bioavailability readout and pharmacodynamics [1]. Moreover, the use of clinically relevant size 3D tissues enable mantaining the real complexity of human biology [2-3]. In conclusion, the combination of the multi OOC platform with human reconstructed gut tissues fluidically connected with human liver models can represent a highly innovative and reliable in vitro model to study the gut-liver axis.
References
1. Fedi et al. Bioengineering 2023
2. Marrella et al. 2021
3. Marzagalli et al. Frontiers in Bioeng and Biotech 2022
4. (Marrella et al. Altex 2020)