How close does a gut-on-a-chip resemble our gut?

How close does a gut-on-a-chip resemble our gut?

Maybe, the first question we should ask is, what is a gut comprised of?

Gut is a surprisingly complex organ. Within it, is a space where enzyme is produced and secreted, food is digested, nutrients are absorbed and the remaining content is being pushed out. Furthermore, various types of cells work together to perform these functions.

Gut-on-a-chip is a version of organ-on-a-chip that aims to create the different physiological conditions of a human gut. Since 2012, there are 23 peer-reviewed publications on gut-on-a-chip on PubMed, a database of medical science publication, so this is still a relatively new area to explore. So, what is a gut-on-a-chip? Why do we develop it? And most importantly, what are the potential use?

Comparison of the structure of a human gut to that of a gut-on-a-chip

As you see in the above diagram, a human gut is comprised of many cell types, including, epithelial cells (the cells that are directly next to the lumen of the gut), endothelial cells (the cells that found in blood vessels) and immune cells, fibroblasts (the cells that are underneath the epithelial cells), nerve cells and muscle cells. Traditionally, these cells are cultured either individually or co-cultured, where 2 types of cells are cultured together. Although these culturing methods have helped us to understand the biochemical characteristics of individual cell types under healthy or disease conditions, these methods do little to help us to understand how different cell types react together to a drug or changes as an organ.

In a gut-on-a-chip, epithelial cells are assembled into a more natural 3D layer (vs. 2D in conventional culture) above an endothelial cell layer, while immune cells were cultured at the bottom chamber. This setup mimics the natural localization of these cell types in the gut. What’s more, microfluidics technology can allow researchers to change culture conditions easily (e.g. addition of a drug), while continuously supply nutrients to the cells and therefore, the system resembling parts of a human gut is sustained and tested for multiple days.

Two research groups have already taken advantage of this system to study viral infection (1) and drug response (2) in human gut, while other groups are trying to improve the technology further. For example, Dr. David Breault’s and Dr. Ingber’s group in Harvard University have successfully derived epithelial cells from stem cells isolated from an intestinal biopsy and cultured them in the chip (3). It can be postulated that in the future, we can test how a patient respond to a certain drug treatment or screen for the optimal treatment strategy using the patient’s personalized gut-on-a-chip.

Another potential use of gut-on-a-chip is to study how the gut microbiota interact with different components of our gut.  At present, most of the study on gut microbiota in humans are observing changes in its relative composition. Gut-on-a-chip will enable us, for the first time, to directly test how microbiota (e.g. bacteria) induce different responses in human cells, especially immune cells.

Gut-on-a-chip is a wonderful tool for scientists to study physiology of our gut, however, there are still limitations to its use. One major drawback is that it cannot support some other important cell types, such as, fibroblasts, nerve cells and muscle cells. These cells play major roles in regulating conditions like strictures, irritable bowel syndrome (IBS) in the gut. Nevertheless, gut-on-a-chip has opened up new avenue for studying the gut as an organ.

(1) Villenave R et al., PLoS One. 2017 Feb 1;12(2):e0169412

(2) Jalili-Firoozinezhad et al., Cell Death Dis. 2018 Feb 14;9(2):223

(3) Kasendra et al., Scientific Reports. 2018 Feb 13;8(1):2871

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