Immunocompetent High-Throughput Gut-on-Chip Model for Intestinal Microbes–Host Interaction Studies

The intestinal microbiota and immune system are separated by an epithelial layer, whose barrier function is crucial for the healthy state of the host, while its impairment, usually associated with inflammation, leads to a variety of pathologies in humans. Different probiotics targeting the preservation of epithelial barrier homeostasis are thus currently being developed. Their selection and validation are a complex process involving in-vitro and in-vivo models. While the former lacks the complexity of the physiological system, the latter often fails to reflect the effect in humans. We used the commercial microfluidic high-throughput device OrganoPlate to set up a Gut-on-Chip model comprising human epithelial and peripheral blood mononuclear cells (PBMC). As a proof-of-concept, we co-cultured several intestinal anaerobic bacteria species in direct contact with the epithelial monolayer for two days to investigate their impact on epithelial barrier integrity and immune response upon induction of inflammation. We demonstrate here that Bacteroides thetaiotaomicron protects the epithelial barrier and dampens CCL2 secretion provoked by LPS-stimulated PBMC. Recapitulating the key features of intestinal inflammation, we suggest that the current Gut-on-Chip model enables an easy-to-use screen of next-generation probiotics and live biotherapeutics with homeostatic and immunomodulatory properties.