The Enterostat: a 3D-printed bioreactor for simulating gut microbiome dynamics

While the gut microbiome is central to host fitness, research in animal systems is limited by challenges in scalability and experimental control. Engineered bioreactors provide a valuable tool for studying microbiome dynamics, but many fail to capture the full anatomical and functional complexity of the gastrointestinal tract. Most existing models focus on either micro-scale features, such as villi and mucosal folds, or macro-scale parameters, such as fluid flow and volume, without integrating both. To address this gap, we introduce the Enterostat, a gut bioreactor platform designed to incorporate structural detail across scales while remaining adaptable to the dimensions and structural complexity of different hosts. We describe the modeling, fabrication, and operation of the Enterostat, and highlight its potential applications in microbiome research. The physical design of the Enterostat gives rise to oxygen gradients and particle retention, conditions that support the establishment and stability of microbial communities. The Enterostat also captures eco-evolutionary responses to antibiotic perturbations, demonstrating its utility for both applied and basic research. Overall, the Enterostat provides a versatile platform for pharmaceutical testing and for investigating how gastrointestinal architecture shapes microbiome composition and function.