Using Gut-on-a-Chip Models to Test Probiotic Therapies on Colitis

September 04, 2018

As many as 70,000 new cases of IBD are diagnosed in the U.S. each year. Professor Hyun Jung Kim is studying how probiotics impact colitis.

Professor Hyun Jung Kim and graduate student Woojung Shin have developed a colitis chip, a microfluidic device that mimics the human colonic environment, to test various probiotic therapies.

Studies suggest there is a growing rise in the number of people living with inflammatory bowel disease (IBD), such as ulcerative colitis or Crohn’s disease. As many as 70,000 new cases are diagnosed in the U.S. each year.

Professor Hyun Jung Kim has received a grant from the Alternatives Research & Development Foundation (ARDF) to study how alteration of the beneficial gut microbiome with probiotics impacts colitis, or inflammation of the inner lining of the colon.

While researchers know that healthy populations of gut bacteria influence gut inflammation, understanding more about how different strains of probiotics impact colitis could greatly improve treatment options.

Conventional methods for testing probiotics and other anti-inflammatory therapies are conducted using animal models. This presents challenges in that anti-inflammatory medications are not metabolized the same way in animal models as they are in humans. Recent studies support that gut bacteria also remarkably perturb the efficacy and toxicity of a swallowed drug compound in the gut. Interestingly, the gut microbiome in an animal, especially for the mouse model typically used, is vastly different from humans.

Kim is engineering a better way to test colitis treatments, without the use of animals.

In collaboration with clinicians from Dell Medical School, Woojung Shin, a third-year graduate student in the Kim lab, will create colonic organoids (colonoids) from the biopsied tissues of a healthy donor. These colonoid models essentially mimic the genetic and phenotypic background of the human gut, but on a much smaller scale. Shin will develop a human colitis chip by growing colonoid-derived gut cells in a microfluidic device the size of a memory stick, which undergoes rhythmical cyclic deformations and fluid shear stress. In this human mini-colon, Shin will cause colitis, inciting inflammation and reducing gut barrier function. Placing the colonoids on a microchip will allow researchers to manipulate the gut microenvironment and introduce different probiotic strains and immune cells to learn more specifically which bacteria improve colitis symptoms.

“A human colitis chip will be a compelling model for screening of new probiotic bacteria, testing of engineered designer probiotics, and validating the efficacy of fecal microbiota transplantation (FMT). We envision that our colitis chip will give us a better understanding of how the IBD progresses and which probiotics could effectively treat it,” says Kim.

The ARDF was established in 1993 and supports the development of alternatives to animal-based methods in science.