Bacteria research could be a gut-punch to inflammatory bowel disease

The group of lifelong intestinal conditions known as inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, significantly impacts digestive health and quality of life for an estimated 2.4 and 3.1 million people in the U.S.

According to Thomas Wood, biotechnology endowed chair and professor of chemical engineering at Penn State, patients with IBD often show elevated levels of pathogenic E. coli—the bacterial strain that can cause serious illness, including food poisoning—in their intestines. An international team of researchers co-led by Wood will investigate the role E. coli plays in the gut and how it may affect intestinal inflammation.

In this Q&A, Wood spoke about the significance of gut bacteria in IBD and how Penn State’s advanced organ-on-chip technologies—which are engineered devices and systems of tissues grown inside microfluidic chips that mimic human physiology—could lead to new diagnostic tools and treatments.

What is known about the relationship between E. coli and IBD?

There are good E. coli that we all have all the time as a relatively minor, beneficial member of our gastrointestinal (GI) tracts. Then there are related, pathogenic E. coli strains that we get from food poisoning, etc., that cause disease. IBD is caused by the pathogenic E. coli and is characterized by not being able to get rid of the bad E. coli. Our work strives to understand how to get rid of the pathogenic E. coli.

In the GI tract, our epithelial cells secrete a sugar-coated protein mucin, which allows our bodies to utilize about a pound of beneficial bacteria, while keeping them from directly touching our epithelial cells that line our guts. So, we have evolved for millions of years to rely on bacteria in our gut but keep them at an “arm’s length” since we do not want them to invade us and enter our bloodstream.

The E. coli pathogens damage the protective mucin layer and allow them to reach epithelial cells, which causes lesions and results in bacterial toxins called Shiga toxins being produced that may result in bloody diarrhea and further damage to the protective lining of the intestine.

Sometimes, antibiotics can be used to help control symptoms, but they are not effective for the young and old since they make the infection worse by inducing Shiga toxin production by the invasive pathogens.

What are the main objectives of this research?

The objective is to be able to study how the pathogens damage mucin and how the commensal—good—bacteria protect mucin when grown in complex communities known as biofilms, which are designed to mimic the human gut environment. We hope to learn how beneficial bacteria interact with disease-causing bacteria, then use that information to make the good bacteria better at getting rid of the IBD-causing bacteria.

One of the methods we will explore is adding DNA that enters the disease-causing bacteria and kills them. The key is determining which of these “DNAzymes” works best to kill the disease-causing bacteria in our GI tract.

What is the organ-on-chip technology that you plan to use? What advantages does it have compared to other research technologies and methods?

The mucin-on-chip device allows us to study our microbiome without using animals, and it allows us to study the complex communities of our guts without disturbing it by using electrochemical signals.

The mucin-on-chip system is a microfluidic tool that uses small channels to mimic the mucin produced by epithelial cells in our GI tracts. The device will allow us to identify the interactions between E. coli and the protective mucin.

What do you hope this research will help accomplish in the future?

We hope this research will lead to effective probiotics that may be taken orally to alter our microbiome—that is, get rid of pathogens—and effectively combat IBD. We also hope to develop techniques to kill the disease-causing bacteria with pieces of DNA.

Hadar Ben-Yoav, of the Department of Biomedical Engineering at Ben-Gurion University, and Ilana Kolodkin-Gal of the Scojen Institute for Synthetic Biology, both in Israel, will co-lead this project.