Gut-liver axis models evolve from static co-cultures to microfluidic systems, review finds

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Frontiers in Medicine Published June 4, 2026 Medically reviewed June 4, 2026 Study authors: Jong Hwan Sung, Raehyun Kim DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Consider that gut-liver axis models are advancing but face technical and biological gaps before clinical translation.

This narrative review examines the evolution of in vitro models for studying the gut-liver axis, ranging from static co-cultures to advanced microfluidic systems. The authors synthesize the current state of the field, highlighting the progression toward more physiologically relevant platforms that better recapitulate interorgan interactions.

Key findings include the identification of several underexplored areas: metabolite-mediated gut-liver crosstalk, immune-mediated interorgan communication, and disease-specific modeling. These gaps represent opportunities for future research to enhance understanding of gut-liver physiology and pathology.

The review also acknowledges technical challenges that remain, particularly in achieving physiologically faithful and reliable integrated platforms. These limitations underscore the difficulty of translating complex in vivo interactions into robust in vitro systems.

While the review provides a useful overview of model systems, it does not offer quantitative comparisons or clinical recommendations. The findings are most relevant for researchers developing or selecting gut-liver axis models, rather than for direct clinical application.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedJun 2026

View Original Abstract ↓

The gut-liver axis maintains metabolic homeostasis and immune regulation through continuous bidirectional communication, and its dysregulation contributes to a range of metabolic, inflammatory, and immune-mediated diseases. Integrated gut-liver axis model systems offer unique tools for dissecting these complex interactions by isolating individual variables that are difficult to disentangle in vivo, while allowing flexible experimental controls over them. Here, we review advances in gut-liver axis models from static co-cultures to microfluidic systems and their applications in pharmacokinetic and mechanistic studies. We identify underexplored areas, including metabolite-mediated gut-liver crosstalk, immune-mediated interorgan communication, and disease-specific modeling, and outline technical challenges to achieving physiologically faithful and reliable integrated platforms. By addressing these challenges, gut-liver axis models will contribute to a mechanistic understanding of gut-liver pathobiology that is difficult to achieve through clinical studies, animal models, or individual organ systems alone.