01529nas a2200157   4500000000100000008004100001260001500042100001600057700001900073245008400092856003800176300001100214490000700225520112500232022001401357       2024                            d  c2024-06-261 aRaehyun Kim1 aJong Hwan Sung00aMicrofluidic gut-axis-on-a-chip models for pharmacokinetic-based disease models  uhttps://doi.org/10.1063/5.0206271  a0315070 v183 aThe low success rate of new drugs transitioning from animal testing to human clinical trials necessitates the development of more accurate and representative in vitro models. Recent advances in multi-organ-on-a-chip technology offer promising avenues for studying complex organ–organ interactions. Gut–liver-on-a-chip systems hold particular promise for mimicking the intricate interplay between the gut and liver, which play crucial roles in nutrient absorption, drug metabolism, detoxification, and immune response. Here, we discuss the key components of the gut–liver axis, including the gut epithelium, liver cells, gut microbiota, and their roles in the organ functions. We then explore the potential of gut–liver-on-a-chip models to replicate the intricate interactions between the two organs for pharmacokinetic studies and their expansion to more complicated multi-organ models. Finally, we provide perspectives and future directions for developing more physiologically relevant gut–liver-axis models for more efficient drug development, studying liver diseases, and personalizing treatment strategies.  a1932-1058