Obesity is a rising worldwide epidemic that increases the risk of developing many diseases like heart disease and diabetes. Despite the medical and diet-based interventions available for obesity today, weight management is still, for many, a daily struggle. Now, scientists may be able to treat obesity using genetically engineered bacteria that can alter the gut microbiota.
Dieting… a word that plagues a great number of the world’s population today, increasingly so, since obesity has become one of the leading epidemics in adults and children worldwide. However, despite the widespread concern with weight management, the number of overweight individuals is rising steadily. What is the cause for this rise in obesity, you may ask, since there are so many methods available nowadays to manage one’s weight? The most likely answer to this question is the continuous lifelong effort that is required in order to achieve and sustain a healthy weight.
So, how can we treat obesity with a more sustainable method that will give long-lasting results?
Scientists at Vanderbilt University in Nashville have now provided a possible solution to this problem, by modifying bacteria to boost weight loss. Gut microbiota have recently been shown to differ between lean and obese mice and humans. Intriguingly, transferring gut bacteria from obese mice to ‘germ free’ mice (lacking microbes in the gut), resulted in dramatically increased body fat and insulin resistance. Considering these observations, changing the gut mircobiota in some way that would reduce hunger, increase satiety and thus prevent weight gain, could potentially provide a long-term, sustainable treatment against obesity.
To accomplish weight loss by altering the gut bacteria, Sean Davies and his colleagues genetically engineered E. coli (Escherichia coli) bacteria to express NAPEs (N-acylphosphatidylethanolamines). NAPEs are precursors of the NAE (N-acylethanolamide) family of lipids that are expressed in the small intestine in response to feeding. Expression of NAPEs in the small intestine after eating leads to reduced food consumption.
In order to see how these modified bacteria would affect obesity, scientists fed mice with an abundantly available high fat diet. They then gave the same mice modified bacteria in their drinking water for 8 weeks. The mice ingesting modified bacteria appeared to be leaner, lighter and with less body fat than their counterparts that had not been fed bacteria expressing NAPEs. Taking into account the lower insulin levels that were also observed and the lack of adverse effects due to the modified bacteria, these mice seemed to be undoubtedly healthier than their peers.
What was even more interesting in this experiment was the fact that after removing the modified bacteria from the drinking water of the mice, they still showed the same effects, even 4 weeks later, despite still being fed a high fat diet. This was indeed very significant, demonstrating the potential long-lasting effect of modified bacteria on obesity!
Last but not least, since obesity in humans is not always only diet-related, the team of Sean Davies decided to also test this method on a genetic model of obesity in mice. What they saw only strengthened their previous observation that modification of the gut bacteria can non-deniably inhibit weight gain.
Can modified bacteria also be used to treat other diseases?
According to the authors, using modified bacteria to deliver therapeutic molecules could potentially be applied to treat other diseases where therapy cannot be administered readily in other ways. Also, being sustainable in the gut after administration, this method could be very patient-friendly, by lifting the burden of taking pills or other substances daily. Another advantage of delivering therapeutic substances straight to the gut is the avoidance of a number of unwanted side effects caused by other types of treatments. Thus, it would seem that modified bacteria could be the way to go in the future for the potential treatment of obesity and a great number of other diseases plaguing the world today.
However, there are also potential downsides to treatments with modified bacteria, as skeptics like to point out. It may be that the dose of modified bacteria required for efficient treatment of a certain disease may be too high, rendering this treatment toxic for patients. Furthermore, it has been shown that even removal of the toxic genes from bacteria can still lead to a certain percentage of mortality in mice. And of course, a major concern with any kind of bacterial therapy is their potential to accumulate mutations. This may lead to the treatment not working properly and possibly extreme bacterial infections.
So, although treatment with modified bacteria may seem like an exciting and easy long-term therapy for obesity and many other diseases, it must still be taken with a pinch of salt until more evidence is provided showing its safety and efficacy for use in patients.
J Clin Invest. 2014;124(8):3391–3406. doi:10.1172/JCI72517