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ICCVAM Biennial Report 2018-2019

Biennial Progress Report 2018-2019 Interagency Coordinating Committee on the Validation of Alternative Methods

Gut-endothelial Barrier Models Incorporating Microbial Colonies

AFRL has developed gut-endothelial barrier models using microfluidic technology. These gut-on-a-chip platforms emulate many of the microstructures (gut epithelial-blood endothelial interactions), morphologies (macro- and micro-villus structures), and functions of the human gut. The dynamic nature of the models provides a robust opportunity for assessing gut-blood barrier integrity, nutrient transport, and host-microbiome interactions. Moreover, a tailored oxygen environment, simulating the low-oxygen conditions seen in the human gut, promotes a more robust microbial colony inclusion. Current investigations are evaluating probiotics, cooperative microbial interactions, and complex microbial community dynamics in the gut-on-a-chip platform. The gut-on-a-chip models are also being combined with brain-on-a-chip models to allow analyses of complex molecular gut-brain axis interactions. These technologies in combination have the potential to enable assessment of operational stress and exposure outcomes due to thermal burden, nutrition, toxin ingestion and digestion, and their corresponding impact on the blood-brain barrier and neuronal activity. Furthermore, identification of molecular targets or pathways for countermeasure development can be developed, matured, and optimized in a human model prior to in vivo testing, thereby limiting animal usage and reducing the cost and time for deployment. Further validation and assessments of these promising capabilities will have to be completed before complete implementation.