Single-celled organisms reprogrammed to create a molecule that becomes a hunger-suppressing lipid through regular metabolism could be the solution to the obesity epidemic, according to new research presented Monday at the annual American Chemical Society (ACS) expo.
In the study, Sean Davies of the Vanderbilt University School of Medicine and his colleagues put the microbes in the water of mice, and those that drank it ate less, had reduced body fat and were even able to stave off diabetes, even when they consumed a diet that has high in fat. The findings indicate that the bacteria could help humans lose weight as well, the authors claim.
Finding therapeutic bacteria
According to the ACS, one-third of all Americans is obese, a condition that could lead to heath ailments such as heart disease, stroke, type 2 diabetes, and some types of cancer. Efforts to battle the epidemic have largely failed, they said, because weight-loss medication and lifestyle changes tend to have modest, short-term effects.
Recent research has suggested that gut microbes could play a key role in determining the risk of obesity and related conditions, indicating that making strategic changes to the gut microbiome may have a positive impact on overall health. Davies noted that one advantage of this approach is that treatment would only need to be administered periodically.
Davies and his team set out to produce a special type of therapeutic bacteria that could live in a person’s gut for at least six months. In contrast to weight-loss drugs that need to be taken at least once a day, this approach would provide sustained treatment over a long period of time, and it would make it so that patients would not need to constantly take weight loss pills.
The researchers used selected N-acyl-phosphatidylethanolamines (NAPEs) as a therapeutic molecule. NAPEs are produced in the small intestine after a meal and are quickly converted into N-acyl-ethanolamines (NAEs), potent appetite-suppressing lipids. They altered the genes of a probiotic bacteria strain so that it would produce NAPEs and added it to the drinking water of mice that typically become obese and develop related health issues when fed a high-fat diet.
NAPEing a difference
When compared to mice that received plain water or water containing non-altered bacteria, those drinking the NAPE-making bacteria gained approximately 15 percent less weight over an eight-week treatment period. Furthermore, their livers and glucose metabolism were better than that of the control mice, and those that received the treatment remained lighter and leaner than control mice for up to three months after the treatments came to an end.
Additional experiments revealed that mice which lacked the enzyme to make NAEs from NAPEs were not helped by the NAPE-making bacteria, but that this issue could be overcome by giving those creatures NAE-making bacteria instead. This led Davies to conclude that “it might be best to use NAE-making bacteria in eventual clinical trials,” especially if his team finds that some individual are unable to produce enough of the enzyme that converts NAPEs to NAEs.
Davies believes that the treatment option “would work very well in humans,” but any human trials face one big obstacle: the potential risk that a treated person could transmit these special bacteria to another by fecal exposure.
“We don’t want individuals to be unintentionally treated without their knowledge,” he explained. “Especially because you could imagine that there might be some individuals, say the very young or old or those with specific diseases, who could be harmed by being exposed to an appetite-suppressing bacteria. So, we are working on genetically modifying the bacteria to significantly reduce its ability to be transmitted.”