A group of researchers has established a protocol for designing a chip that mimics the microenvironment of the human intestine.
This protocol, which was developed by researchers at UT and the Wyss Institute at Harvard University, was published in the Journal of Visualized Experiments on Aug. 30. This simulated microenvironment includes the microbiome, or the community of bacteria that resides inside the digestive tract. These bacteria impact a person’s health and determine how they digest their food.
Each individual’s microbiome contains a unique combination of bacteria and other microorganisms. Researchers study microbiomes to learn more about gastrointestinal diseases, but according to Hyun Jung Kim, first author of the gut-on-a-chip protocol and assistant professor of biomedical engineering, current methods of culturing them in Petri dishes fail to accurately simulate the environment inside the intestine.
“The plastic dishes are not identical at all with the very soft, highly organized system in the body — normally the cells cultured on those systems are not fully differentiated and functional,” Kim said. “Another thing is that our body system is always under mechanical forces, like stretching, bowel movements, peristalsis. Normally for plates, there’s no shear stress, no flow, no mechanical strain.”
To fix this, Kim helped design a device referred to as a “human-gut-on-a-chip.” This device is made out of silicone and has two parallel microchannels; one contains intestinal cells and the other mimics capillary blood vessels inside the intestines. When appropriate intestinal cells are introduced to the chip, the chip performs different functions, including digestion and absorption. Researchers can also use the chip to study responses to disease by adding immune cells and bacteria that cause disease.
The gut-on-a-chip interface is not restricted to mimicking intestinal microbiomes. It can also be used to replicate other microbiomes, such as those on human skin or genitals. Kim said a better understanding of microbiomes brings scientists closer to understanding disease.
“Technologies like gut-on-a-chip are an exciting development in microbiome research because they allow scientists to do precise experiments that just aren’t possible with other approaches,” said Chad Smith, a UT postdoctoral fellow and microbiome researcher.
Kim said he hopes this device will advance personalized medicine and replace the use of animal models in drug testing, which are labor-intensive and ethically questionable.
“If you have 100 of the devices that are holding patient samples with colorectal cancer or irritable bowel syndrome, if you make multiple ‘avatar’ chips for each patient, you can test different doses or types of drugs in personalized approaches,” Kim said.
Kim said the chip system also simplifies research on diseases that involve interactions between microbiota and the immune system, because experimental factors are easier to control in the chip.
Kim recently received a grant to create Crohn’s disease on a chip. The funding allows him to make multiple chips that mimic the intestines of patients with Crohn’s disease. He said this research can be used to test different dosages of medicine and multiple therapeutic interventions for treating an individual.
“You have 10 times as many bacterial cells as body cells. We are just beginning to understand the role of microbiomes and how they interact with our host system,” Kim said. “Maintaining balance between microbiomes and host system is important. If you can precisely predict responses [to imbalances], it will be very powerful in understanding the etiology of diseases.”