Ingestible “Electroceutical” Capsule Boosts Appetite Hormone Levels

A new study in animal models has shown how an electrical capsule can stimulate stomach cells to produce the appetite-stimulating hormone ghrelin, which may one day help to treat conditions involving nausea or appetite loss. The research is published in Science Robotics.

Regulating digestion

The gastrointestinal (GI) tract is part of our digestive system, responsible for the breakdown and absorption of nutrients from what we eat and drink. It has its own nervous system – the enteric nervous system – that controls all aspects of digestion, such as the movement of food through the GI tract.

In some cases, disorders of the enteric nervous system can cause problems with digestion. For example, a disorder of the stomach nerves – known as gastroparesis – can slow down the movement of food through the GI tract. Electrical stimulation of the stomach can improve the symptoms of this condition using a pacemaker-like device surgically implanted in the stomach.

This electrical device was thought to help contract the stomach and push food through the GI tract, though it later emerged that movement was not significantly improved by the device. Instead, the researchers in the current study hypothesized that electrical stimulation may boost the release of ghrelin, a hormone that promotes hunger and reduces nausea, and developed an electrical capsule to test their hypothesis.

Electrical stimulation boosts ghrelin levels

Using animal models, the researchers from Massachusetts Institute of Technology (MIT) tested the ability of electrical stimulation to boost ghrelin production in the stomach using a probe, demonstrating that 20 minutes of electrical stimulation significantly increased levels of ghrelin in the blood without any adverse effects.

Next, the researchers refined their approach by developing an electrical capsule that could be swallowed and temporarily reside in the stomach. They designed the capsule with a grooved surface, inspired by the skin of the Australian thorny devil lizard, which transports water that lands on its skin towards its mouth via capillary action. With its grooved design and hydrophilic coating, the capsule wicks away fluid from the stomach tissue and allows electrodes in the device to make contact with the tissue.

Experiments administering the capsule into the stomachs of pigs showed that the device was also successful in producing large spikes in ghrelin levels in the bloodstream.

“As far as we know, this is the first example of using electrical stimuli through an ingestible device to increase endogenous levels of hormones in the body, like ghrelin. And so, it has this effect of utilizing the body's own systems rather than introducing external agents,” said Dr. Khalil Ramadi, co-lead author of the paper and assistant professor of bioengineering at New York University Tandon School of Engineering.

The researchers also found that the vagus nerve, which controls digestion, must be intact for the electrical stimulation to be effective. This suggests that the electrical pulses may be transmitted to the brain via the vagus nerve, resulting in signals that instruct endocrine cells in the stomach to produce ghrelin.

Trials in humans on the horizon

The prototype device used in the current study used a constant electric current, but future versions are planned that can be wirelessly turned on and off.

“As far as we know, this is the first example of using electrical stimuli through an ingestible device to increase endogenous levels of hormones in the body, like ghrelin. And so, it has this effect of utilizing the body's own systems rather than introducing external agents,” said Ramadi.

“This study helps establish electrical stimulation by ingestible electroceuticals as a mode of triggering hormone release via the GI tract,” added Dr. Giovanni Traverso, associate professor of mechanical engineering at MIT, gastroenterologist at Brigham and Women’s Hospital and 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.”

Traverso also suggests that the simplicity of the device could enable trials in humans in as soon as the next three years, and that development of the device for patients could complement or even replace existing drugs used to decrease nausea and stimulate appetite in humans.

Reference: Ramadi KB, McRae JC, Selsing G, et al. Bioinspired, ingestible electroceutical capsules for hunger-regulating hormone modulation. Sci Adv. 2023. doi: 10.1126/scirobotics.ade9676 

This article is a rework of a press release issued by Massachusetts Institute of Technology. Material has been edited for length and content.