Nan Yang
Registered Member
Chinese team aims to put ‘smart’ diabetes probiotic on US shelves within 2 years
The engineered probiotic, named Gift, can sense high blood sugar and automatically release the glucose-lowering hormone GLP-1
Chinese researchers have engineered a probiotic that could make diabetes care as simple as drinking a cup of yogurt or swallowing a capsule.
The “smart” bacterium, designed to sense high blood sugar and automatically release a glucose-lowering hormone, performed on par with the blockbuster drug Ozempic in animal tests, according to a study published in Nature last week.
The team at East China Normal University in Shanghai has already filed patents and is now scaling up production to meet pharmaceutical standards for the US and European markets.
“If all goes well, the probiotic is expected to be available in the United States in the form of a health supplement in about two years,” lead scientist Ye Haifeng said in an interview with China Science Daily on Thursday.
Diabetes is one of the most common chronic metabolic diseases. More than 530 million adults worldwide have diabetes, and this number could increase to over 850 million by 2050. Patients must take oral medications or inject insulin to control their blood sugar.
After oral administration, the probiotic remains “silent” when blood glucose levels are normal and automatically triggers a glucose-lowering mechanism when levels rise.
“We show efficacy from the engineered probiotics for glycaemic control in multiple diabetic mouse and non-human primate models, showing that long-term oral administration drives clear improvements in lipid profiles, while also attenuating development of multiple diabetic complications,” Ye’s team wrote in the paper.
Since returning to China from ETH Zurich in 2011, Ye has focused on engineering cells to reduce the burden of long-term medication or injections for diabetic patients.
Previously, Ye and his team implanted genetically modified mammalian cells into diabetic mice then used blue light to activate GLP-1 expression – the production of a gut-derived, blood-sugar-regulating hormone. They published the findings in a 2011 paper in Science, another top-tier journal.
However, this system has limitations as it requires external signals, such as blue light, to start the intervention.
The probiotic has proved safe and effective in diabetic mice and monkeys. Photo: Handout
In the Thursday interview, Ye said he hoped his latest innovation would be smarter by adapting to changes in blood glucose levels in the human body, just like the body’s own blood sugar regulation system.
Compared with modified cells, orally administered, engineered probiotics offer additional advantages: greater safety, convenient administration and the ability to keep the gut microbiome balanced.
Ye’s team selected a probiotic called E coli Nissle 1917 as the base cell – a strain that is safe for humans.
On this base cell, the team implanted a protein that acts like a glucose detector and the gene that encodes GLP-1, which functions as a drug production line.
The former is the HexR protein derived from Pseudomonas putida bacteria. This protein remains closed when blood glucose levels are normal and opens immediately when levels rise.
When the protein opens, the gene is switched on, producing the hormone GLP-1, which promotes insulin secretion.
This engineered probiotic has been named Gift, short for glucose-sensing and functional response probiotic. Ye told China Science Daily he hoped it could “become a gift for diabetes patients”.
Researchers have tested the probiotic on mice and monkeys.
In a classic type 2 diabetes mouse model, serum GLP-1 levels peaked two to four hours after a single oral dose of Gift, with a significant reduction in blood glucose.
After 30 consecutive days of daily administration, the rodents’ fasting blood glucose, glucose tolerance and insulin tolerance improved significantly, while their glycated haemoglobin (HbA1c) levels decreased markedly.
Long-term oral administration of Gift also alleviated hepatic steatosis, or fatty liver disease, kidney injury and inflammation of the colon in mice.
In monkeys, serum GLP-1 and plasma insulin levels rose rapidly after a single oral dose of Gift, with the glucose-lowering effect lasting up to three days. Throughout the entire five-week observation period, the primates’ blood sugar levels remained stable and controllable.
To assess Gift’s potential for clinical use, the team also conducted a head-to-head comparison with Ozempic. The results showed Gift’s glucose-lowering effects were comparable to those of the weight-loss wonder drug.
Ye’s team has applied for a patent for Gift. They are now focusing on safety improvements and optimising the production process to meet Good Manufacturing Practice standards, with the aim of entering the US and European markets.
However, Gift’s strategic value “goes beyond diabetes”, Ye said in an interview published on East China Normal University’s website on Friday.
“Its glucose-sensing module and therapeutic module are independent of each other, meaning that both the sensing element and the therapeutic output can be replaced, forming a modular, programmable next-generation ‘smart drug’ development framework,” he said, adding that this could be extended to metabolic diseases such as obesity and steatosis.
The engineered probiotic, named Gift, can sense high blood sugar and automatically release the glucose-lowering hormone GLP-1
Chinese researchers have engineered a probiotic that could make diabetes care as simple as drinking a cup of yogurt or swallowing a capsule.
The “smart” bacterium, designed to sense high blood sugar and automatically release a glucose-lowering hormone, performed on par with the blockbuster drug Ozempic in animal tests, according to a study published in Nature last week.
The team at East China Normal University in Shanghai has already filed patents and is now scaling up production to meet pharmaceutical standards for the US and European markets.
“If all goes well, the probiotic is expected to be available in the United States in the form of a health supplement in about two years,” lead scientist Ye Haifeng said in an interview with China Science Daily on Thursday.
Diabetes is one of the most common chronic metabolic diseases. More than 530 million adults worldwide have diabetes, and this number could increase to over 850 million by 2050. Patients must take oral medications or inject insulin to control their blood sugar.
After oral administration, the probiotic remains “silent” when blood glucose levels are normal and automatically triggers a glucose-lowering mechanism when levels rise.
“We show efficacy from the engineered probiotics for glycaemic control in multiple diabetic mouse and non-human primate models, showing that long-term oral administration drives clear improvements in lipid profiles, while also attenuating development of multiple diabetic complications,” Ye’s team wrote in the paper.
Since returning to China from ETH Zurich in 2011, Ye has focused on engineering cells to reduce the burden of long-term medication or injections for diabetic patients.
Previously, Ye and his team implanted genetically modified mammalian cells into diabetic mice then used blue light to activate GLP-1 expression – the production of a gut-derived, blood-sugar-regulating hormone. They published the findings in a 2011 paper in Science, another top-tier journal.
However, this system has limitations as it requires external signals, such as blue light, to start the intervention.
The probiotic has proved safe and effective in diabetic mice and monkeys. Photo: Handout
In the Thursday interview, Ye said he hoped his latest innovation would be smarter by adapting to changes in blood glucose levels in the human body, just like the body’s own blood sugar regulation system.
Compared with modified cells, orally administered, engineered probiotics offer additional advantages: greater safety, convenient administration and the ability to keep the gut microbiome balanced.
Ye’s team selected a probiotic called E coli Nissle 1917 as the base cell – a strain that is safe for humans.
On this base cell, the team implanted a protein that acts like a glucose detector and the gene that encodes GLP-1, which functions as a drug production line.
The former is the HexR protein derived from Pseudomonas putida bacteria. This protein remains closed when blood glucose levels are normal and opens immediately when levels rise.
When the protein opens, the gene is switched on, producing the hormone GLP-1, which promotes insulin secretion.
This engineered probiotic has been named Gift, short for glucose-sensing and functional response probiotic. Ye told China Science Daily he hoped it could “become a gift for diabetes patients”.
Researchers have tested the probiotic on mice and monkeys.
In a classic type 2 diabetes mouse model, serum GLP-1 levels peaked two to four hours after a single oral dose of Gift, with a significant reduction in blood glucose.
After 30 consecutive days of daily administration, the rodents’ fasting blood glucose, glucose tolerance and insulin tolerance improved significantly, while their glycated haemoglobin (HbA1c) levels decreased markedly.
Long-term oral administration of Gift also alleviated hepatic steatosis, or fatty liver disease, kidney injury and inflammation of the colon in mice.
In monkeys, serum GLP-1 and plasma insulin levels rose rapidly after a single oral dose of Gift, with the glucose-lowering effect lasting up to three days. Throughout the entire five-week observation period, the primates’ blood sugar levels remained stable and controllable.
To assess Gift’s potential for clinical use, the team also conducted a head-to-head comparison with Ozempic. The results showed Gift’s glucose-lowering effects were comparable to those of the weight-loss wonder drug.
Ye’s team has applied for a patent for Gift. They are now focusing on safety improvements and optimising the production process to meet Good Manufacturing Practice standards, with the aim of entering the US and European markets.
However, Gift’s strategic value “goes beyond diabetes”, Ye said in an interview published on East China Normal University’s website on Friday.
“Its glucose-sensing module and therapeutic module are independent of each other, meaning that both the sensing element and the therapeutic output can be replaced, forming a modular, programmable next-generation ‘smart drug’ development framework,” he said, adding that this could be extended to metabolic diseases such as obesity and steatosis.
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