“Mice that received the bacteria making the appetite suppressing drug NAPE weighed 10-12% less than the untreated mice, had 35% less overall body fat and had 56% less fat in their liver,” senior investigator Sean Davies told NutraIngredients.
The team genetically modified the E.coli Nissle strain, which has been used as a probiotic treatment for diarrhoea for nearly a century, to produce a lipid compound called NAPE.
“Previous research had shown that NAPE was made by the small intestine when people ate a meal, and that it could send signals to the brain that would reduce appetite and body weight,” said Davies.
He said there was evidence that NAPE production may be reduced in obese people, provoking reduced feelings of satiety and therefore a greater likelihood of overeating.
“We thought that if we could get the gut bacteria to make enough NAPE in addition to what was made by the intestine, it would help suppress appetite,” he continued.
The scientists added the NAPE-producing bacteria to the drinking water of mice fed a high fat diet for eight weeks. Mice that received the modified bacteria had dramatically lower food intake, body fat, insulin resistance and fatty liver compared to the mice receiving the control bacteria.
These effects lasted for at least four weeks after the NAPE-producing bacteria were removed from the drinking water.
“Our results demonstrate that incorporation of appropriately modified bacteria into the gut microbiota has potential as an effective strategy to inhibit the development of metabolic disorders,” wrote the researchers.
The obesity battle
Davies pointed out that this was early stage research in mice not humans, but admitted, “it looks promising”.
“I wouldn’t say it will be a complete ‘cure’ for obesity but it could be an effective treatment for helping people reach a body weight that prevents many of the problems associated with obesity, like diabetes.”
The EU’s heavy regulation of GMOs means that it would be some time – if ever – before such a probiotic strain would be authorised for sale in the region. But could findings such as these, which demonstrate the positive potential of genetic modification, go some way to softening the anti-GM sentiment that pervades Europe?
“Obviously the more we can show that the use of therapeutic bacteria is safe and effective, the more likely we will increase acceptance of their use. Europe has generally been ahead of the US in the use of probiotics, so that might be something that can be built on,” suggested Davies.
The investigators are working on strategies to address regulatory issues related to containing the bacteria, because, as Davies explained: “Preclinical studies in animals will need to show that these organisms won’t spread to untreated individuals and that they don’t cause harm to animals with less functional immune systems where it might be more likely for the bacteria to leave their home in the gastrointestinal tract and invade the blood stream.”
The Journal of Clinical Investigation
‘Incorporation of therapeutically modified bacteria into gut microbiota inhibits obesity’
Authors: Zhongyi Chen, Lilu Guo, Yongqin Zhang, Rosemary L. Walzem, Julie S. Pendergast, Richard L. Printz, Lindsey C. Morris, Elena Matafonova, Xavier Stien, Li Kang, Denis Coulon, Owen P. McGuinness, Kevin D. Niswender and Sean S. Davies