A better understanding of the gut-brain axis may lead to new treatments for neurological disorders

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" (https://www.nature.com/articles/s41378-020-00184-4), 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" (https://ieeexplore.ieee.org/document/9123494), 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" (https://www.nature.com/articles/s41378-020-00208-z).

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).

Source:
Journal reference:

Rajasekaran, P. R., et al. (2020) 3D-Printed electrochemical sensor-integrated transwell systems. Microsystems & Nanoengineering. doi.org/10.1038/s41378-020-00208-z.

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