Is It All in Your Head—or in Your Gut? Or Both?

Anyone who has ever experienced “butterflies in the stomach” before a big presentation won’t be surprised to learn there is an actual physical connection responsible for that fluttering sensation. 

Neuroscientists and medical professionals call it the “gut-brain-axis” (GBA), and a better understanding of it could lead to treatments and cures for a range of chronic auto-immune inflammatory diseases like irritable bowel syndrome and rheumatoid arthritis, and also for neurological mood disorders like depression and anxiety.

The problem is that up until now, patients’ reports of their own symptoms were what physicians have primarily had to work with in detecting GBA-related disorders. But now, supported by $1 million in National Science Foundation funding, University of Maryland (UMD) engineers, neuroscientists, microbiologists and physicists are making significant progress in developing objective measurements to dramatically improve diagnosis and take an enormous burden off patients to accurately describe their own symptoms.

“We are converging neuroscience, molecular signaling and micro-nano devices and systems. This enables us to measure and investigate data at the interface of each junction of a simulated GBA platform—cell to cell, cell to molecule, molecule to nerve—and develop engineering methodologies to analyze and interpret it,” said Professor Reza Ghodssi of the Department of Electrical and Computer Engineering and the Institute for Systems Research (ISR).

The key to the research is “biomarkers”—substances that indicate a disorder’s presence. For the GBA, that biomarker is believed to be the neurotransmitter serotonin, which spurs the nervous system into action via the vagus nerve, the physical connector between the brain and the colon. 

The team is working to develop a platform that can monitor and model the real-time processing of gut microbiome serotonin activity. Its goal is to one day package the platform into an ingestible capsule capable of detecting, treating and monitoring GBA diseases.

Three recent published papers by the team detail the progress in detecting serotonin, assessing its neurological effects and sensing minute changes to the gut epithelium:

• In one published last month in the Nature journal Microsystems and Nanoengineering, the team developed a platform that provides access to the specific site of serotonin production, important because serotonin is secreted from the bottoms of cells. An innovative porous membrane with an integrated serotonin sensor on which a model of the gut lining can be grown allowed researchers to access both top and bottom sides of the cell culture. The authors are bioengineering Ph.D. student Ashley Chapin, former ISR postdoctoral researcher Pradeep Ramiah Rajasekaran, David N. Quan Ph.D. ’15, materials science and engineering Professor Liangbing Hu, psychology Associate Professor Jens Herberholz, bioengineering Professor William Bentley and Ghodssi.
• In another paper, published online in the IEEE Journal of Microelectromechanical Systems, builds on the findings of the first: the researchers developed the serotonin measuring platform further so it could assess serotonin’s neurological effects. The paper was written by Chapin, electrical and computer engineering Ph.D. student Jinjing Han, neuroscience and cognitive science Ph.D. student Ta-Wen Ho, Herberholz and Ghodssi.
• The concept, design and use for the entire biomonitoring platform is described in a third paper published online this month in Microsystems and Nanoengineering and written by Rajasekaran, Chapin, Quan, Herberholz, Bentley and Ghodssi. This paper delves into the development of the 3D-printed housing for the capsule, the maintenance of a healthy lab-on-a-chip gut cell culture, and the evaluation of the two types of sensors integrated on the cell culture membrane. The dual sensors provide feedback about multiple components of the system, including the portions that model the gut lining’s permeability, which is a strong indicator of disease, and its serotonin release, a measure of its communication with the nervous system. 

The work builds on ingestible medical device expertise that has been developed in the UMD MEMS Sensors and Actuators Laboratory, the Fischell Department of Bioengineering and the Brain and Behavior Initiative.