Calming the gut

An extensive network of neurones lines the gut. This neural tissue is filled with important neurotransmitters, allowing the gut to do a lot more than simply digest food or cause nervous butterflies. The ‘second brain’ in our belly connects to the big one in our skull, helping to determine our mental state, while also contributing to certain diseases.

Inflammatory Bowel Disease (IBD) is a chronic and debilitating disorder that can lead to potentially life-threatening complications.

Florey Institute researchers are helping to develop a bionic device that could potentially treat IBD and bring relief to more than 75,000 Australians.

As they do, they’re pushing at the frontiers of the burgeoning field of “electroceuticals”, the use of bio-electronic implants to stimulate nerves in the body, in this case in the gut. The US Defense Department is funding the team with a $6 million grant.

Professor John Furness, the lead researcher on the project, recalls the excitement he shared when the Director of the Bionics Institute, Professor Robert Shepherd, came to him with the idea for the project.

“I was fascinated by the challenge,” John says. “Could we develop a way of stimulating nerves to deal with IBD?”

Currently IBD, which includes Crohn’s disease and ulcerative colitis, is treated with a range of drugs and is moderated by dietary approaches. However, the medications have side-effects and tend to fail over time. Eventually many patients have to undergo surgery but even after surgery, disease, and notably Crohn’s, can recur.

A multi-skilled team of five was formed for the project: Florey neurophysiologist Professor Robin McAllen; Director of Biomedical Engineering at University of Melbourne Professor David Grayden; surgeon and Professor of Surgery at the Austin Hospital Professor Bob Jones; and Professors Furness and Shepherd. John is an expert in the field of digestive physiology and nutrition, and is often invited to address conferences here and overseas on these topics.

The team successfully bid for funding from the Defense Advanced Research Projects Agency (DARPA) in the US as part of a call for research into electric stimulation to treat disease by modulating the activity of peripheral nerves. The “blue sky” proposal was the only project out of the seven funded by DARPA that was outside the US.

DARPA was interested in the technology’s potential to help the many combat veterans affected by IBD – US veterans have twice the frequency of IBD as the general population, possibly as a side-effect of post traumatic disorder.

“Treating the stress is helpful but it doesn’t always work,” John says. “Once the disease is established, you’ve got abnormal tissue so removing the stress doesn’t get rid of the disease – you need to find another way,” he says.

The bionic device is implanted under the skin with a lead to electrodes wrapped around the 2mm wide branches of the vagus nerve in the abdomen. The vagus nerve runs from the brainstem, branching out to many different organs, including the gut. A controller the size of a smart phone outside the body transmits signals to the device.

Researchers elsewhere had previously tried stimulating the vagus nerve in the neck to try to manage the inflammation caused by IBD but had encountered side-effects in the heart and larynx. The Florey team decided to use a novel approach to avoid these complications by stimulating the nerve in the abdomen instead.

Pre-clinical trials are underway and clinical trials are due to start in 2019.

“This is a possible solution to a problem that remains unsolved by drug treatment. Finding another approach to it could be extremely important for IBD.

“Crohn’s and ulcerative colitis are terrible conditions because they cause the bowel lining to erode. It may bleed or perforate and the tissue disruption can lead to cancer.”

In Crohn’s disease the lining of the digestive system or gut is inflamed. Ulcerative colitis usually occurs in the rectum, lower part of the colon and sometimes the entire large intestine or colon.

Similar devices could potentially be used to treat other diseases such as arthritis and respiratory illnesses.

The project has had an important spin-off. The team has invented a device that measures the effects of inflammation in the colon in real time – a potentially valuable innovation to the field. Currently, inflammatory bowel diseases are difficult to track as they flare up, repair, relapse and go into remission then flare up again.

“It’s hard to get a good idea of where you are in the disease process, which is pretty important to treatment and adjusting treatment.

“If we can monitor the inflammation successfully we can modify the therapy. Usually you can’t do that, you use indirect ways of understanding the intensity of the disease, such as how the patient is feeling or you have to take invasive measures like biopsies to access what’s going on.”

The process will be fully automated, reducing the need for frequent consultations with the clinicians.

“This invention is a good diagnostic and monitoring tool. I think it’s going to be pretty important for gastroenterology.”

The device, patented last year, has been tested in rats and sheep. It is currently being refined for use in people.

The success of this project emphasises the value of multidisciplinary research to produce significant outcomes, according to Professor Rob Shepherd. “In this case clinicians, biomedical scientists and engineers are working in close collaboration to develop new therapies,” Rob says.