An ingestible capsule that delivers electrical current can stimulate the release of the hormone ghrelin. It might help.Credit: Courtesy of Researcher
This device, which uses electricity to boost the stomach’s production of hormones, may help relieve nausea and reduce loss of appetite.
Hormones released by the stomach, such as ghrelin, play an important role in stimulating appetite. These hormones are produced by endocrine cells, part of the enteric nervous system that control hunger, nausea, and satiety.
Researchers have developed an ingestible capsule called FLASH (Fluid-wicking Active Stimulation and Hormone modulation) that can electronically stimulate the hunger-regulating hormone ghrelin in pigs. Inspired by the fluid-wicking skin of the Australian thorny devil lizard, the capsule emits electronic signals and moves through the body, eventually being excreted. This proof-of-concept study demonstrates the potential of ingestible electroceuticals for treating gastrointestinal, neuropsychiatric, and metabolic disorders. The team plans to continue researching for human application and explore treatment options for eating disorders and metabolic diseases. Credit: Giancarlo Traverso (GT Reel Productions)
“This study helps establish electrical stimulation by ingestible electroceuticals as a mode of triggering hormone release via the GI tract,” says Giovanni Traverso, an associate professor of mechanical engineering at MIT, a gastroenterologist at Brigham and Women’s Hospital, and the senior author of the study. “We show one example of how we’re able to engage with the stomach mucosa and release hormones, and we anticipate that this could be used in other sites in the GI tract that we haven’t explored here.”
Khalil Ramadi SM ’16, PhD ’19, a graduate of the Department of Mechanical Engineering and the Harvard-MIT Program in Health Sciences and Technology who is now an assistant professor of bioengineering at the New York University (NYU) Tandon School of Engineering and the director of the Laboratory for Advanced Neuroengineering and Translational Medicine at NYU Abu Dhabi, and James McRae, an MIT graduate student, are the lead authors of the paper, which was published on April 26 in the journal Science Robotics.
Electrical stimulation
The enteric nervous system controls all aspects of digestion, including the movement of food through the GI tract. Some patients with gastroparesis, a disorder of the stomach nerves 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 provoke the stomach into contracting, which would help push food along. However, it was later found that while the treatment does help patients feel better, it affected motility to a lesser degree. The MIT team hypothesized that the electrical stimulation of the stomach might be leading to the release of ghrelin, which is known to promote hunger and reduce feelings of nausea.
The capsule surface consists of grooves with a hydrophilic coating. These grooves function as channels that draw fluid away from the stomach tissue. Credit: Courtesy of the researchers
To test that hypothesis, the researchers used an electrical probe to deliver electrical stimulation in the stomachs of animals. They found that after 20 minutes of stimulation, ghrelin levels in the bloodstream were considerably elevated. They also found that electrical stimulation did not lead to any significant inflammation or other adverse effects.
Once they established that electrical stimulation was provoking ghrelin release, the researchers set out to see if they could achieve 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 electrodes on the capsule can contact the stomach tissue, which are coated with fluid.
To create a drier surface that electrodes can interact with, the researchers gave their capsule a grooved surface that wicks fluid away from the electrodes. The surface they designed is inspired by the skin of the Australian thorny devil lizard, which uses ridged scales to collect water. When the lizard touches water with any part of its skin, water is transported by capillary action along the channels to the lizard’s mouth.
“We were inspired to incorporate surface textures and patterns on the outside of this capsule,” says McRae. “Its surface can manage fluids that could potentially prevent the electrodes from touching the stomach tissue, so we can deliver reliable electrical stimulation.”
The capsule surface consists of grooves with a hydrophilic coating. These grooves act as channels that draw fluid away from the stomach tissue. Inside the device are battery-powered electronics that generate a current that flows between the electrodes on the surface of the capsule. In the prototype used in the study, the current was always flowing, but the researchers say future versions may be designed to turn the current on and off wirelessly.
hormone boost
Researchers tested the capsules by administering them to the stomachs of large animals and found that the capsules produced significant spikes in ghrelin levels in the bloodstream.
“To our knowledge, it is the first example of using electrical stimulation via an ingestible device to increase endogenous levels of hormones like ghrelin in the body. It has the effect of using the body’s own system instead of the body itself,” says Ramadi.
Inside the device are battery-powered electronics that generate a current that flows between the electrodes on the surface of the capsule.Credit: Courtesy of Researcher
Researchers have found that the vagus nerve, which controls digestion, must be intact for this stimulation to work. They theorize that electrical pulses are transmitted to the brain via the vagus nerve and stimulate endocrine cells in the stomach to produce ghrelin.
Traverso’s lab now plans to explore using this approach in other parts of the gastrointestinal tract, and researchers hope to test the device on human patients within the next three years. . If developed for use in human patients, this type of therapy would replace some of the existing drugs used to prevent nausea and stimulate appetite in people with cachexia or anorexia. or complement it, researchers say.
“Because it’s a relatively simple device, we think it’s something that humans can take relatively quickly,” says Traverso.
For more information on this breakthrough device, see Ingestible Electroceutical Taming Hunger Hormone.
Reference: “Bio-Inspired, Fluid-Wicking, Ingestible Electroceutical Capsules for Hunger-Regulating Hormone Regulation”, Khalil B. Ramadi, James C. McRae, George Selsing, Arnold Su, Rafael Fernandes, Maela Hickling, Brandon Rios, Sahab Babaee, Seokkee Min, Declan Gwynne, Neil Zixun Jia, Aleyah Aragon, Keiko Ishida, Johannes Kuosmanen, Josh Jenkins, Alison Hayward, Ken Kamrin, Giovanni Traverso, 26 April 2023, Available here. science robotics.
DOI: 10.1126/scirobotics.ade9676
This work was funded by the National Cancer Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, the Department of Engineering, New York University Abu Dhabi, the National Science Foundation Graduate Research Fellowship, and a Koch Institute Supporting (Core) grant from Novo. I was. Nordisk, and the Department of Mechanical Engineering at MIT.
