Ingestible capsule that could help demystify the gut-brain axis

Date:
October 15, 2020
Source:
University of Maryland
Summary:
A team of experts from engineering, neuroscience, applied
microbiology, and physics has been making headway on building a
platform that can monitor and model the real-time processing of
gut microbiome serotonin activity.



FULL STORY ========================================================================== Anyone who has experienced "butterflies in the stomach" before giving
a big presentation will be unsurprised to learn there is a physical
connection between their gut and their brain. Neuroscientists and medical professionals call this connection the "gut-brain axis" (GBA); a better understanding of the GBA could lead to the development of treatments
and cures for neurological disorders such as depression and anxiety,
as well as for a range of chronic auto-immune inflammatory diseases such
as irritable bowel syndrome (IBS) and rheumatoid arthritis.


========================================================================== Right now, these conditions and diseases are primarily diagnosed
by patients' reports of their symptoms. However, neuroscientists and
doctors are investigating the GBA in order to find so-called "biomarkers"
for these diseases. In the case of the GBA, that biomarker is likely
serotonin.

By targeting this complex connection between the gut and the brain,
researchers hope they can uncover the role of the gut microbiome in both
gut and brain disorders. With an easily identifiable biomarker such as serotonin, there may be some way to measure how dysfunction in the gut microbiome affects the GBA signaling pathways. Having tools that could
increase understanding, help with disease diagnosis, and offer insight
into how diet and nutrition impacts mental health would be extremely
valuable.

With $1 million in National Science Foundation funding, a team of
University of Maryland experts from engineering, neuroscience, applied microbiology, and physics has been making headway on building a platform
that can monitor and model the real-time processing of gut microbiome
serotonin activity. Three new published papers detail the progress of the
work, which includes innovations in detecting serotonin, assessing its neurological effects, and sensing minute changes to the gut epithelium.

In "Electrochemical Measurement of Serotonin by Au-CNT Electrodes
Fabricated on Porous Cell Culture Membranes" the team developed
a platform that provides access to the specific site of serotonin
production. The platform included a porous membrane with an integrated serotonin sensor on which a model of the gut lining can be grown. This innovation allowed researchers to access both top and bottom sides of
the cell culture -- important because serotonin is secreted from the
bottoms of cells. The work is the first to demonstrate a feasible method
for detection of redox molecules, such as serotonin, directly on a porous
and flexible cell culture substrate. It grants superior access to cell- released molecules and creates a controllable model gut environment to
perform groundbreaking GBA research without the need to perform invasive procedures on humans or animals.

The team's second paper, "A Hybrid Biomonitoring System for Gut-Neuron Communication" builds on the findings of the first: the researchers
developed the serotonin measuring platform further so it could assess serotonin's neurological effects. By adding and integrating a dissected crayfish nerve model with the gut lining model, the team created a
gut-neuron interface that can electrophysiologically assess nerve response
to the electrochemically detected serotonin. This advance enables the
study of molecular signaling between gut and nerve cells, making possible real-time monitoring of both GBA tissues for the first time.

Finally, the concept, design, and use for the entire biomonitoring
platform is described in a third paper, "3D Printed Electrochemical Sensor Integrated Transwell Systems." This paper delves into the development of
the 3D-printed housing, 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 are particularly important because they provide feedback
about multiple components of the system -- namely, the portions that
model the gut lining's permeability (a strong indicator of disease)
and its serotonin release (a measure of communication with the nervous
system). Alongside the electrochemical sensor -- evaluated using a
standard redox molecule ferrocene dimethanol -- an impedance sensor was
used to monitor cell growth and coverage over the membrane. Using both
these sensors would allow monitoring of a gut cell culture under various environmental and dietary conditions. It also would enable researchers
to evaluate changes to barrier permeability (a strong indicator of
disease), and serotonin release (a measure of communication with the
nervous system).


========================================================================== Story Source: Materials provided by University_of_Maryland. Note:
Content may be edited for style and length.


========================================================================== Journal References:
1. Pradeep Ramiah Rajasekaran, Ashley Augustiny Chapin, David N. Quan,
Jens
Herberholz, William E. Bentley, Reza Ghodssi. 3D-Printed
electrochemical sensor-integrated transwell systems. Microsystems &
Nanoengineering, 2020; 6 (1) DOI: 10.1038/s41378-020-00208-z
2. Ashley A. Chapin, Pradeep R. Rajasekaran, David N. Quan,
Liangbing Hu,
Jens Herberholz, William E. Bentley, Reza Ghodssi. Electrochemical
measurement of serotonin by Au-CNT electrodes fabricated on
microporous cell culture membranes. Microsystems & Nanoengineering,
2020; 6 (1) DOI: 10.1038/s41378-020-00184-4
3. Ashley A. Chapin, Jinjing Han, Ta-Wen Ho, Jens Herberholz,
Reza Ghodssi.

A Hybrid Biomonitoring System for Gut-Neuron Communication. Journal
of Microelectromechanical Systems, 2020; 29 (5): 727 DOI: 10.1109/
JMEMS.2020.3000392 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/10/201015173128.htm

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