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<p>The gut brain axis (GBA) is a complex, bidirectional communication network integrating neural, hormonal, immune, and microbial signals to regulate appetite and metabolism. As obesity and metabolic diseases rise globally, a deeper understanding of gut–brain interactions is urgently needed. However, conventional models—animal experiments and static cell cultures—fail to fully recapitulate human physiology and dynamic gut–brain signaling. Organ-on-a-chip (OoC) platforms have emerged as promising in vitro alternatives that integrate human cells, fluid flow, and mechanical forces to mimic organ-level functions. This review explores the current landscape of OoC technologies applied to appetite regulation, focusing on gut-on-chip, brain-on-chip, and integrated gut–brain-axis-on-chip systems. These models enable real-time monitoring of nutrient sensing, hormone secretion (e.g., GLP-1, PYY), and neuronal responses to gut-derived signals, while incorporating microbiota, immune components, and blood–brain barrier dynamics. We highlight key applications in studying microbial metabolites, nutrient-specific satiety signals, obesity-associated dysregulation, and therapeutic screening. Furthermore, we discuss technical challenges such as maintaining long-term co-culture with microbiota, inter-organ signal fidelity, and personalized modeling using patient-derived cells. By critically assessing recent advances and future directions, we propose that OoC technologies offer a transformative framework for decoding gut–brain signaling pathways and advancing precision medicine in nutrition and metabolic disorders.</p>

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Organ-on-a-Chip Models for Studying Gut–Brain Axis and Appetite Regulation

  • 期刊论文

  • 发表日期：

    2025年10月7日

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  • Sehoon Jeong,
  • Sunhye Lee

摘要

The gut brain axis (GBA) is a complex, bidirectional communication network integrating neural, hormonal, immune, and microbial signals to regulate appetite and metabolism. As obesity and metabolic diseases rise globally, a deeper understanding of gut–brain interactions is urgently needed. However, conventional models—animal experiments and static cell cultures—fail to fully recapitulate human physiology and dynamic gut–brain signaling. Organ-on-a-chip (OoC) platforms have emerged as promising in vitro alternatives that integrate human cells, fluid flow, and mechanical forces to mimic organ-level functions. This review explores the current landscape of OoC technologies applied to appetite regulation, focusing on gut-on-chip, brain-on-chip, and integrated gut–brain-axis-on-chip systems. These models enable real-time monitoring of nutrient sensing, hormone secretion (e.g., GLP-1, PYY), and neuronal responses to gut-derived signals, while incorporating microbiota, immune components, and blood–brain barrier dynamics. We highlight key applications in studying microbial metabolites, nutrient-specific satiety signals, obesity-associated dysregulation, and therapeutic screening. Furthermore, we discuss technical challenges such as maintaining long-term co-culture with microbiota, inter-organ signal fidelity, and personalized modeling using patient-derived cells. By critically assessing recent advances and future directions, we propose that OoC technologies offer a transformative framework for decoding gut–brain signaling pathways and advancing precision medicine in nutrition and metabolic disorders.