Assistant Staff Cleveland Clinic Cleveland, Ohio, United States
Introduction:: The human gut microbiome is crucial in maintaining metabolic functions and intestinal homeostasis. Indeed, imbalances in the intestinal microbiota can result in various diseases, such as inflammatory bowel disease (IBD), colorectal cancer (CRC), infectious diseases, and complex disorders associated with the gut-brain axis. Unfortunately, there is currently a lack of reliable models to study the interactions between the host and microbiome over time. While human intestinal organoids have been developed, they are limited by their enclosed lumen and inability to accurately mimic host-microbiome interactions.
Materials and Methods:: To address this challenge, we have developed a microengineered Gut-on-a-chip model that enables the study of intestinal physiology, 3D morphogenesis, accurate oxygen control, mechanodynamic bowel movement, and longitudinal host-microbiome interactions. Moreover, the accessibility and modularity of this model allow us to identify specific disease triggers by recoupling the uncoupled complex factors germane to disease development in a spatiotemporal manner.
Results, Conclusions, and Discussions:: In a pathomimetic human intestinal inflammation-on-a-chip model, we discovered that the intact epithelial barrier is necessary and sufficient to maintain the homeostatic tolerance of the gut under complex host-microbiome crosstalks. Additionally, our Gut-on-a-chip model allows for patient-specific simulations of host responses to various microbial stimulations in both IBD and CRC Chips. Hence, our personalized disease models may offer a translational breakthrough in investigating the etiology and therapeutic interventions for multifactorial gastrointestinal diseases.
