Organ on a chip tracks gut-to-brain toxins for Parkinson’s clues

The model simulated how gut neurotoxins can trigger brain cell death as seen in Parkinson’s disease.

Outlined in a proof-of-concept study from the Quadram Institute, the universities of Hull and Essex, and the UK Health Security Agency (UKHSA), the work is detailed in Biomicrofluidics, demonstrating how the system replicates the gut-brain

bidirectional communication network that links the gastrointestinal tract and the nervous system of the brain.

The scientists say their research will have the capacity to provide insights into understanding of Parkinson’s’ disease and more neurodegenerative conditions.

Parkinson’s affects millions of people worldwide, destroying cerebral nerve cells but also triggering non-motor symptoms elsewhere.

The protein accumulations characteristic of brain cell damage caused by the disease can present in the gut years before diagnosis, together with changes in gut microbiome.

Miniature microphysiological systems (MPS), or organ-on-chip technology, permit the growth of human cells or tissues in appropriate conditions to mimic how they look, behave and communicate in situ.

A seed start-up grant enabled the University of Essex’s enabled Dr Ben Skinner together with the UK Health Security Agency’s (UKHSA) Dr Simon Funnell to work with the Quadram Institute’s professor Simon Carding and Drs Emily Jones and Aimee Parker, as well as professor John Greenman and Dr Lydia Baldwin from Hull York Medical School’s Centre for Biomedicine based at the University of Hull on the project.

This approach could revolutionise our understanding of neurological disorders, paving the way for more effective treatments and ultimately improving the lives of millions affected by these conditionFunnell said that the death of his mother from Parkinson’s inspired him to commit to innovative research in the field

Dr Emily Jones, Quadram institute

“This collaborative research has applications outside of Parkinson’s disease and UKHSA is working to use this tool to better understand the impact of infectious diseases on the body and evaluate treatments and vaccines,” he explained.

To create the gut-brain MPS, two devices were combined in series and connected via tubing representing the blood flow. In the first device, a layer of cells represented the gut lining form a selectively permeable barrier between the contents of the gut and the rest of the body. In the second, human-derived brain neuronal cells of a type known to be susceptible to neurotoxins were cultured. 

A chance meeting with Skinner at a University of Essex lab challenge day culminated in more than five years’ work on the project by the pair.

For the proof-of-concept study, the neurotoxin was introduced into the gut, and was seen to kill off the brain cells, without affecting the cells of the gut lining as it passed across them.

Added the Quadram Institute’s Jones: “By allowing us to study human-derived cells in an interconnected model, we aim to gain deeper insights into disease mechanisms and potentially identify new therapeutic targets that can protect against neuronal inflammation and cell death.

“This approach could revolutionise our understanding of neurological disorders, paving the way for more effective treatments and ultimately improving the lives of millions affected by these conditions.”

The simplified MPS was designed by the University of Hull for easier use without specialist training, and to be applied to various disorders, reducing dependence on animal-based research and enabling it for high-containment laboratory settings involving dangerous infections.

“Each time our devices are used by colleagues to answer different clinical questions we learn how to improve and adapt them in terms of capabilities, robustness and ease of use; we haven’t finished yet” said Prof John Greenman from the Centre for Biomedicine (HYMS) at the University of Hull.

Professor Isabel Oliver, UKHSA chief scientific officer at the UK Health Security Agency said organ on chip tech was improving understanding of the impact of viruses on the human body.

“We’ve already developed this technique to look at the impact of COVID-19 on the lungs and we are now working to expand this tool to study other organs and how they are impacted by COVID-19 and other infections,” she stated.

The research was funded by the Economic and Social Research Council (UKHSA and University of Essex, Public Health Challenge Lab) and Biotechnology and Biological Sciences Research Council (QIB), both part of UKRI.