Dissecting Gut‐Microbial Community Interactions using a Gut Microbiome‐on‐a‐Chip

• Published in: Advanced science 2024-05, Vol.11 (20), p.e2302113-n/a
• Main Authors: Lee, Jeeyeon, Menon, Nishanth, Lim, Chwee Teck
• Format: Article
• Language: English
• Subjects: Bacteria; Behavior; Caco-2 Cells; Cell culture; Disease; Gastrointestinal Microbiome - physiology; gut microbiota; gut‐microbial community interactions; gut‐on‐a‐chip; Humans; Influence; Interfaces; inter‐microbial interactions; Lab-On-A-Chip Devices; Microbiome; Microbiota; organ‐on‐a‐chip; Roles; Visualization
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202302113

While the human gut microbiota has a significant impact on gut health and disease, understanding of the roles of gut microbes, interactions, and collective impact of gut microbes on various aspects of human gut health is limited by the lack of suitable in vitro model system that can accurately replicate gut‐like environment and enable the close visualization on causal and mechanistic relationships between microbial constitutents and the gut. , In this study, we present a scalable Gut Microbiome‐on‐a‐Chip (GMoC) with great imaging capability and scalability, providing a physiologically relevant dynamic gut‐microbes interfaces. This chip features a reproducible 3D stratified gut epithelium derived from Caco‐2 cells (µGut), mimicking key intestinal architecture, functions, and cellular complexity, providing a physiolocially relevant gut environment for microbes residing in the gut. Incorporating tumorigenic bacteria, enterotoxigenic Bacteroides fragilis (ETBF), into the GMoC enable the observation of pathogenic behaviors of ETBF, leading to µGut disruption and pro‐tumorigenic signaling activations. Pre‐treating the µGut with a beneficial gut microbe Lactobacillus spp., effectively prevent ETBF‐mediated gut pathogenesis, preserving the healthy state of the µGut through competition‐mediated colonization resistance. The GMoC holds potential as a valuable tool for exploring unknown roles of gut microbes in microbe‐induced pathogenesis and microbe‐based therapeutic development. A scalable Gut Microbiome‐on‐a‐Chip (GMoC) that faithfully recreates a physiologically relevant dynamic gut‐microbes interface is presented. The GMoC provide a biomimetic 3D gut model (μGut), closely mimicking key features of the intesine and enabling the visualization of gut microbial behaviors, interactions, and their collective influence on gut health and disease through high‐magnification imaging. The GMoC can offer valuable insights into dissecting microbe‐induced pathogenesis and developing microbe‐based therapeutics to enhance overall gut health.