H.J. Kim
Cleveland Clinic,
United States
Keywords: Gut-on-a-chip, Host-microbe interaction, Intestinal organoid, Disease modeling
Summary:
The human gut microbiome plays a critical role in maintaining intestinal health, influencing disease progression, and regulating overall metabolic functions. Dysbiosis in the gut microbiota can drive disorders such as inflammatory bowel disease (IBD), Crohn's disease, ulcerative colitis, colorectal cancer (CRC), and infectious diseases, as well as disrupt the gut-brain axis. Despite advances in human intestinal organoid models, existing systems often fall short of accurately capturing the complex, continuous interactions between host and microbiome. To bridge this gap, our team has developed a human Gut-on-a-Chip microphysiological system that authentically replicates key aspects of intestinal physiology, including mechanodynamic bowel movements, three-dimensional (3D) morphogenesis, controlled oxygen levels, and sustained host-microbiome interactions. The accessibility and modularity of this microengineered Gut-on-a-Chip platform allow for precise investigation into specific disease mechanisms, reestablishing the interconnected complexities essential for modeling disease progression over time. In our pathomimetic human intestinal inflammation-on-a-chip model, we discovered that an intact epithelial barrier is both necessary and sufficient to sustain homeostatic tolerance in the gut under dynamic host-microbiome interactions. Additionally, integrating patient-derived organoid epithelium within the Gut-on-a-Chip enables the simulation of patient-specific host responses to diverse microbial stimuli in our IBD and CRC Chip models. This breakthrough in personalized disease modeling offers transformative potential for identifying underlying causes and therapeutic targets in multifactorial gastrointestinal diseases. Our research holds the promise to fundamentally advance our understanding and treatment of these complex disorders.