For people living with diabetes, managing blood sugar can mean constantly watching the clock, keeping meals and medications on schedule and staying alert to changes in glucose levels. While little can be done about timed meals, researchers have developed a biological system that detects rising blood sugar levels and automatically responds by releasing medication to bring glucose back down.
In a recent study published in Nature, scientists from the Shanghai Academy of Natural Sciences (SANS) in China developed an oral living drug, GIFT, made from engineered probiotic bacteria. The bacteria carry a built-in molecular glucose sensor, created using a gene circuit controlled by a sensor protein called HexR.
Once swallowed, the probiotics temporarily reside in the intestine. When the sensor detects blood sugar rising above normal levels, it switches on therapeutic genes in the bacteria that produce and release GLP-1, a hormone that triggers insulin release to lower blood sugar.
When we eat high-sugar items like cola or chocolate, blood sugar rises sharply, and mice’s metabolism reacts similarly. However, when mice that received a dose of the probiotic were fed these high-sugar foods, the probiotic detected the sugar spike and prevented extreme blood sugar surges. The living drug also restored healthy blood sugar balance, significantly reduced insulin resistance and improved cholesterol profiles in naturally diabetic monkeys that received probiotics every three days for five weeks.
GIFT that keeps giving on demand
Diabetes isn’t just high blood sugar; it’s a long-term disease that, when left uncontrolled, can trigger metabolic diseases, cardiovascular issues, kidney disease and hormone imbalances.
Over the past few years, diabetes care has found another ally alongside a healthy diet and exercise: GLP-1 receptor agonists. These drugs mimic the natural hormone GLP-1, which helps regulate blood sugar by boosting insulin release while blocking glucagon, the hormone that raises blood sugar.
The challenge is that modern diabetes injections, such as semaglutide, deliver a constant, high dose of medicine into the body, which over time could lead to a range of adverse reactions. Having a smart system that can deliver precise, on-demand dosing only when a person’s blood sugar is high could help revolutionize diabetes care.
The researchers wanted to achieve something similar with their new oral living drug. So they built a glucose-sensing genetic switch inside a harmless probiotic gut bacterium called Escherichia coli Nissle 1917, or EcN. They placed a synthetic promoter called PHexR next to a standard promoter to control gene activity. When there’s no glucose in the gut, a protein called HexR binds to this promoter, which keeps the circuit switched off.
However, when glucose enters the bacteria, the cell’s metabolism converts it into a molecule called KDPG, which binds to HexR and forces it to release the promoter, signaling the bacteria to start producing the therapeutic hormone GLP-1.
To protect the bacteria from immediate harm in the gut, the team coated them with FDA-approved materials: tannic acid and poloxamer 188. Experiments on mice revealed that this successfully extended the time the bacteria remained active in the intestines from 8 hours to 36 hours.
When the team gave diabetic mice GIFT, the probiotic sensed when blood sugar levels rose above a normal threshold and responded by releasing the therapeutic hormone GLP-1, which triggered insulin release to lower blood sugar. The probiotic automatically shut off hormone production once blood sugar returned to a healthy range.
After 30 days of daily treatment, diabetic mice given the probiotic showed a significant reduction in fat mass and weight gain. The treatment also lowered harmful blood fats, including triglycerides and total cholesterol, while improving metabolism and showing protective effects on the liver and kidneys.
The researchers then turned to naturally diabetic monkeys, an important testing step because nonhuman primates are genetically very close to humans. A single oral dose of the probiotic boosted insulin and kept their blood sugar under control for up to three days.
The researchers also compared the probiotic directly with semaglutide, a GLP-1 drug. Unlike semaglutide, the probiotic appeared to reduce the risk of low blood sugar when combined with insulin. Over two months, mice treated with semaglutide lost lean muscle tissue, while those given the probiotic preserved or slightly increased their lean muscle mass.
The results show that GIFT is a promising step toward smart, self-regulating therapies that sense the body’s needs and respond automatically. The next challenge is turning this into a treatment that can be used in the clinic, which will require safety trials, stability testing and regulatory approval because it involves a genetically modified organism. https://www.universetoday.com/articles/earths-magnetosphere-might-not-protect-us-from-superstorms-after-all
Recent Comments