Uncovering Why Drugs Work Differently for Different People

Illinois Institute of Technology Associate Professor of Biomedical Engineering Abhinav Bhushan has received a National Science Foundation CAREER award to create better intestinal organoids and use them to investigate how bacteria living in the gut impact the absorption of drugs into the body.

This area of study may hold the key to the longstanding question of why there is so much variation in how people respond to drugs, with the potential for major impact on patient care as Americans take more than 200 million oral pills daily. 

Bhushan says all attempts at creating intestinal organoids, in vitro devices mimicking the intestinal environment, so far have had repeatability issues.

“When you do experiments for drugs with these organoids, if you take some tests today, some tests tomorrow, and some tests the next day, there is a lot of variability in the results,” he says. 

He believes that adding the bacteria that typically inhabit the intestine to the organoids will help provide biochemical cues as the cells develop that will make it more in line with how intestinal cells actually function in the body. 

But there’s a reason this hasn’t been done before: it’s no small feat. Intestinal cells require oxygen to live while most gut bacteria die in the presence of oxygen, making it a challenge to build a device that simulates this environment.

Fortunately, this is not the first time Bhushan has resolved this challenge. His lab has developed an innovative microfluidic device that holds both gut bacteria and cells in separate areas according to their needs, but are still able to chemically signal to each other through a mucus layer, similar to how they are separated in the body.

“The roots of this project are at Illinois Tech,” says Bhushan, referring to the Nayar Prize II competition funding that allowed him to start developing the project.

He has applied the device to testing treatments for colon cancer through a National Institutes of Health award, and now will engineer a new device to carry out the work on organoids and drug absorption. 

While previous studies have shown that some bacteria are able to break down or transform some drugs, at a fundamental level, it’s not well understood how the presence of different bacteria in the gut would transform the amount of a drug that is absorbed into the body.

“A big contributing reason to why people respond differently to drugs is that they have different gut bacteria,” says Bhushan. 

He says there may be a range of possible ways to improve drug performance depending on what the tests show, such as the development of a probiotic that can be taken with an existing drug to improve its effectiveness.

Bacteria have been found in almost every part of the body, so Bhushan says he expects the further development of his microfluidic device could help researchers studying the lungs, skin, ovaries, tumors, and other organ systems too. 

Bhushan says the project has broader impact beyond the research as it will provide uniquely multidisciplinary research opportunities for Illinois Tech undergraduate and graduate students, spanning microbiology, drug development, mathematical modeling, and microfluidic device design and creation. He is also planning a series of workshops spanning these topics.

“That’s one of the most exciting parts of the project for me,” he says.

Disclaimer: “Research reported in this publication was supported by the National Science Foundation under Award Number 2240045. This content is solely the responsibility of the authors and does not necessarily represent the official views of the National Science Foundation.”

Abhinav Bhushan, “CAREER: Microbial Control of Intestinal Organoids Development and Function,” National Science Foundation; Award Number 2240045.

Image: Associate Professor of Biomedical Engineering Abhinav Bhushan.