Hormones released by the stomach, such as ghrelin, play a key role in stimulating appetite. These hormones are produced by endocrine cells that are part of the enteric nervous system, which controls hunger, nausea, and feelings of satiety.
MIT engineers have now shown that they can stimulate these endocrine cells to produce ghrelin, using an ingestible capsule that sends an electrical current to the cells. This approach could prove useful for the treatment of conditions involving nausea or loss of appetite, such as cachexia (loss of body mass that can occur in patients with cancer or other chronic diseases).
In animal tests, the researchers demonstrated that this “electroceutical” capsule could significantly increase the production of ghrelin in the stomach. They believe this approach could also be adapted to deliver electrical stimulation to other parts of the gastrointestinal tract.
“This study helps establish electrical stimulation by ingestible electroceuticals as a way to trigger hormone release through the gastrointestinal tract,” says Giovanni Traverso, associate professor of mechanical engineering at MIT, gastroenterologist at Brigham and Women’s Hospital, and author study principal. study. “We show an example of how we can interact with the lining of the stomach and release hormones, and we anticipate that this could be used at other sites in the GI tract that we have not explored here.”
Khalil Ramadi SM ’16, PhD ’19, graduate of the Department of Mechanical Engineering and the Harvard-MIT Program in Health Sciences and Technology, who is now Assistant Professor of Bioengineering at the NYU Tandon School of Engineering and Director of the Laboratory for Neuroengineering Advanced and Translational Medicine at NYU Abu Dhabi, and James McRae, an MIT graduate student, are the lead authors of the paper, which appears today in robotics science.
electrical stimulation
The enteric nervous system controls all aspects of digestion, including the movement of food through the gastrointestinal tract. Some patients with gastroparesis, a nerve disorder of the stomach that leads to very slow movement of food, have shown symptomatic improvement after electrical stimulation generated by a pacemaker-like device that can be surgically implanted in the stomach.
Doctors had theorized that the electrical stimulation would cause the stomach to contract, helping to push the food out. However, it was later discovered that while the treatment helped patients feel better, it affected motility to a lesser degree. The MIT team hypothesized that electrical stimulation of the stomach might be triggering the release of ghrelin, which is known to promote hunger and reduce feelings of nausea.
To test that hypothesis, the researchers used an electrical probe to deliver electrical stimulation to the animals’ stomachs. They found that after 20 minutes of stimulation, ghrelin levels in the bloodstream rose considerably. They also found that electrical stimulation did not lead to any significant inflammation or other adverse effects.
Once they established that the electrical stimulation was causing the release of ghrelin, the researchers set out to see if they could accomplish the same thing using a device that could be swallowed and temporarily reside in the stomach. One of the main challenges in designing such a device is ensuring that the capsule’s electrodes can come into contact with stomach tissue, which is lined with fluid.
To create a drier surface for the electrodes to interact with, the researchers gave their capsule a grooved surface that absorbs liquid from the electrodes. The surface they designed is inspired by the skin of the Australian spiny devil lizard, which uses ribbed scales to collect water. When the lizard touches the water with any part of its skin, the water is transported by capillarity along the channels to the lizard’s mouth.
“We were inspired by that to incorporate surface textures and patterns on the exterior of this capsule,” says McRae. “That surface can handle fluid that might prevent the electrodes from touching tissue in the stomach, so it can reliably provide electrical stimulation.”
The capsule surface consists of grooves with a hydrophilic coating. These grooves function as channels that draw fluid from the stomach tissue. Inside the device are battery-powered electronics that produce an electrical current that flows through electrodes on the capsule’s surface. In the prototype used in this study, the current runs constantly, but future versions could be designed so that the current can be turned on and off wirelessly, according to the researchers.
hormone boost
Researchers tested their capsule by administering it into the stomach of large animals and found that the capsule produced a substantial increase in ghrelin levels in the bloodstream.
“To our knowledge, this is the first example of the use of electrical stimuli via an ingestible device to increase endogenous levels of hormones in the body, such as ghrelin. And therefore it has the effect of using the systems themselves of the body instead of introducing external hormones. agents,” says Ramadi.
The researchers found that for this stimulation to work, the vagus nerve, which controls digestion, must be intact. They theorize that electrical pulses are transmitted to the brain via the vagus nerve, which then stimulates endocrine cells in the stomach to produce ghrelin.
Traverso’s lab now plans to explore the use of this approach in other parts of the GI tract, and the researchers hope to test the device in human patients within the next three years. If developed for use in human patients, this type of treatment could potentially replace or complement some of the existing drugs used to prevent nausea and stimulate appetite in people with cachexia or anorexia, the researchers say.
“It’s a relatively simple device, so we think it’s something we can introduce to humans on a relatively quick time scale,” Traverso says.
The research was funded by the Koch Institute Support Grant (Core) from the National Cancer Institute, the National Institute for Diabetes and Digestive and Kidney Diseases, Division of Engineering, New York University in Abu Dhabi, a grant research program for graduates of the National Science Foundation, Novo Nordisk, and the MIT Department of Mechanical Engineering.
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