When you eat a large meal, your stomach signals your brain to create a feeling of fullness, which helps you realize it's time to stop eating. A stomach full of fluid can also convey these messages, which is why dieters are often advised to drink a glass of water before eating. MIT engineers have now come up with a new way to exploit this phenomenon, consuming a digestible capsule that vibrates within the stomach. These vibrations activate the same stretch receptors that cause the stomach to expand, creating an illusory feeling of fullness.

The researchers found that giving the pills to animals 20 minutes before eating not only stimulated the release of hormones that signal satiety, but also reduced the animals' food intake by about 40 percent. Scientists still have much to learn about the mechanisms that affect body weight, but if further research shows the technology can be used safely in humans, the pill could offer a minimally invasive way to treat obesity, the researchers said.

"For people who want to lose weight or control their appetite, it could be really interesting to take it before each meal because it would provide an option that minimizes the side effects we see with other drug treatments," said Shriya Srinivasan, Ph.D., 20, an assistant professor of bioengineering at Harvard University.

Srinivasan is the lead author of the new study, published today in the journal Science Advances. Giovanni Traverso, an associate professor of mechanical engineering at MIT and a gastroenterologist at Brigham and Women's Hospital, is the paper's senior author.

satiety

When the stomach expands, special cells called mechanoreceptors sense the stretch and send signals to the brain via the vagus nerve. As a result, the brain stimulates the production of insulin as well as hormones such as c-peptide, PyY, and GLP-1. All of these hormones work together to help people digest food, feel full, and stop eating. At the same time, levels of ghrelin, a hormone that promotes hunger, decrease.

While Srinivasan was a graduate student at MIT, he became interested in the idea of ​​controlling this process by artificially stretching mechanoreceptors in the stomach through vibrations. Previous research has shown that applying vibration to a muscle can create the perception that the muscle is stretched farther than it actually is.

"I wondered if we could activate stretch receptors in the stomach by vibrating them so that they feel the entire stomach is expanding, creating an illusion of expansion that could modulate hormones and eating patterns," Srinivasan said.

As a postdoc at MIT's Koch Institute for Integrative Cancer Research, Srinivasan worked closely with the Traverso lab, which developed many new ways to take oral drugs and electronic devices. In the study, Srinivasan and a team of researchers including Traverso designed a multivitamin-sized capsule that included a vibrating element. When the pill, powered by a small silver oxide battery, reaches the stomach, acidic gastric juices dissolve the membrane covering the capsule, completing the electronic circuit that activates the vibrating motor.

In an animal study, researchers found that once the pill starts vibrating, it activates mechanoreceptors that send signals to the brain by stimulating the vagus nerve. The researchers tracked hormone levels during the vibrations of the device and found that they mirrored hormone release patterns after eating, even when the animals were fasting.

The researchers then tested the effects of this stimulation on the animals' appetite. They found that when the pill was activated for about 20 minutes before the animals were given food, they consumed an average of 40 percent less food than when the pill was not activated. The animals also gained weight more slowly while taking the vibrating pills.

"The behavioral changes are impressive using endogenous systems rather than any exogenous treatment. We have the potential to overcome some of the challenges and costs associated with biologic drug delivery by modulating the enteric nervous system," Traverso said.

The pill is currently designed to vibrate for about 30 minutes after entering the stomach, but the researchers plan to explore the possibility of making it stay in the stomach longer, where it can wirelessly turn on and off as needed. In animal experiments, the pill passed through the digestive tract within four to five days.

The study also found that when the pills were in the animals' digestive tracts, they showed no signs of obstruction, perforation or other negative effects.

an alternative

Researchers say the pill could offer an alternative to current treatments for obesity. Non-medical interventions, such as diet and exercise, are not always effective, and many existing medical interventions are quite invasive and traumatic. These include gastric bypass surgery and gastric balloon surgery, which are no longer widely used in the United States due to safety concerns.

Medications such as GLP-1 agonists can also help with weight loss, but most require injections, which for many people is unaffordable. Srinivasan said the manufacturing cost of MIT's capsules makes it accessible to people who don't have access to more expensive treatment options.

"For many people, some of the more effective treatments for obesity are prohibitively expensive. At scale, our device can be produced at a fairly cost-effective price point, and I'm interested to see how this will change care and treatment for people in health settings around the world who may not have access to some of the more complex or expensive options available today."

The researchers now plan to explore ways to scale up production of the capsules for clinical trials in humans. Studies like this are important to learn more about the safety of this device, as well as determining the best time to take the capsules before meals and how often they need to be taken.

Other authors of the paper include Amro Alshareef, Alexandria Hwang, Ceara Byrne, Johannes Kuosmann, Keiko Ishida, Joshua Jenkins, Sabrina Liu, Wiam Abdalla Mohammed Madani, Alison Hayward and Niora Fabian.

The research was funded by the National Institutes of Health, Novo Nordisk, the MIT Department of Mechanical Engineering, a Schmidt Science Fellowship, and the National Science Foundation.