02074nas a2200193   4500000000100000008004100001260001400042100001600056700002000072700001900092700002200111700001600133245007600149856005500225300001100280490000700291520156800298022001401866       2025                            d  c2025-3-071 aHyehyun Kim1 aGregory Girardi1 aAllison Pickle1 aTestaverde S. Kim1 aErkin Seker00aMicrofluidic tools to model, monitor, and modulate the gut–brain axis  uhttps://pmc.ncbi.nlm.nih.gov/articles/PMC11890156/  a0213010 v193 aThe gut–brain axis (GBA) connects the gastrointestinal tract and the central nervous system (CNS) via the peripheral nervous system and humoral (e.g., circulatory and lymphatic system) routes. The GBA comprises a sophisticated interaction between various mammalian cells, gut microbiota, and systemic factors. This interaction shapes homeostatic and pathophysiological processes and plays an important role in the etiology of many disorders including neuropsychiatric conditions. However, studying the underlying processes of GBA in vivo, where numerous confounding factors exist, is challenging. Furthermore, conventional in vitro models fall short of capturing the GBA anatomy and physiology. Microfluidic platforms with integrated sensors and actuators are uniquely positioned to enhance in vitro models by representing the anatomical layout of cells and allowing to monitor and modulate the biological processes with high spatiotemporal resolution. Here, we first briefly describe microfluidic technologies and their utility in modeling the CNS, vagus nerve, gut epithelial barrier, blood–brain barrier, and their interactions. We then discuss the challenges and opportunities for each model, including the use of induced pluripotent stem cells and incorporation of sensors and actuator modalities to enhance the capabilities of these models. We conclude by envisioning research directions that can help in making the microfluidics-based GBA models better-suited to provide mechanistic insight into pathophysiological processes and screening therapeutics.  a1932-1058