Gut-on-a-chip models for dissecting the gut microbiology and physiology

Microfluidic technologies have been extensively investigated in recent years for developing organ-on-a-chip-devices as robust in vitro models aiming to recapitulate organ 3D topography and its physicochemical cues. Among these attempts, an important research front has focused on simulating the physiology of the gut, an organ with a distinct cellular composition featuring a plethora of microbial and human cells that mutually mediate critical body functions. This research has led to innovative approaches to model fluid flow, mechanical forces, and oxygen gradients, which are all important developmental cues of the gut physiological system. A myriad of studies has demonstrated that gut-on-a-chip models reinforce a prolonged coculture of microbiota and human cells with genotypic and phenotypic responses that closely mimic the in vivo data. Accordingly, the excellent organ mimicry offered by gut-on-a-chips has fueled numerous investigations on the clinical and industrial applications of these devices in recent years. In this review, we outline various gut-on-a-chip designs, particularly focusing on different configurations used to coculture the microbiome and various human intestinal cells. We then elaborate on different approaches that have been adopted to model key physiochemical stimuli and explore how these models have been beneficial to understanding gut pathophysiology and testing therapeutic interventions.