Dynamics of Spatial Organization of Bacterial Communities in a Tunable Flow Gut Microbiome‐on‐a‐Chip

The human intestine, a biomechanically active organ, generates cyclic mechanical forces crucial for maintaining its health and functions. Yet, the physiological impact of these forces on gut microbiota dynamics remains largely unexplored. In this study, we investigate how cyclic intestinal motility influences the dynamics of gut microbial communities within a 3D gut-like structure (µGut). To enable the study, a tunable flow Gut Microbiome-on-a-Chip (tfGMoC) is developed that recapitulates the cyclic expansion and compression of intestinal motility while allowing high-magnification imaging of microbial communities within a 3D stratified, biomimetic gut epithelium. Using deep learning-based microbial analysis, it is found that hydrodynamic forces organize microbial communities by promoting distinct spatial exploration behaviors in microorganisms with varying motility characteristics. Empirical evidence demonstrates the impact of gut motility forces in maintaining a balanced gut microbial composition, enhancing both the diversity and stability of the community - key factors for a healthy microbiome. This study, leveraging the new tfGMoC platform, uncovers previously unknown effects of intestinal motility on modulating gut microbial behaviors and community organizations. This will be critical for a deeper understanding of host-microbiome interactions in the emerging field of microbiome therapeutics.