"NAPE seemed like a great compound to try since it's something that the host normally produces," Davies said.
The investigators added the NAPE-producing bacteria to the drinking water of mice eating 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 mice receiving control bacteria.
They found that these protective effects persisted for at least four weeks after the NAPE-producing bacteria were removed from the drinking water. And even 12 weeks after the modified bacteria were removed, the treated mice still had much lower body weight and body fat compared to the control mice. Active bacteria no longer persisted after about six weeks.
"We still haven't achieved our ultimate goal, which would be to do one treatment and then never have to administer the bacteria again," Davies said. "Six weeks is pretty long to have active bacteria, and the animals are still less obese 12 weeks out.
"This paper provides a proof of concept," he said. "Clearly, we can get enough bacteria to persist in the gut and have a sustained effect. We would like for that effect to last longer."
Davies noted that the researchers also observed effects of the compounds in the liver, suggesting that it may be possible to use modified bacteria to deliver therapeutics beyond the gut.
The investigators are currently working on strategies to address regulatory issues related to containing the bacteria, for example by knocking out genes required for the bacteria to live outside the treated host.
|Contact: Leigh MacMillan|
Vanderbilt University Medical Center