Researchers at Vanderbilt University in Nashville, Tennessee have raised hopes for the possibility of developing of a probiotic to treat obesity and other chronic diseases. The team inhibited weight gain, insulin resistance and various other negative health effects of a high-fat diet in mice by modifying bacteria to produce a therapeutic compound in the gut.
With previous studies having demonstrated that so-called "good" bacteria naturally found in the gut plays a role in obesity, diabetes and cardiovascular disease, Sean Davies, Ph.D., an assistant professor of Pharmacology at Vanderbilt, set out to see if it was possible to manipulate gut microbiota to promote health.
Davies and his team started with E. coli Nissle 1917, which is a safe bacterial strain that colonizes the human gut and has been used as a probiotic treatment for diarrhea for nearly 100 years. They then genetically modified the strain to produce a lipid compound called NAPE, which is normally synthesized in the small intestine when it processes fat and suppresses appetite.
After the NAPE-producing bacteria were added to the drinking water of mice fed a high-fat diet for eight weeks, the researchers found they had dramatically lower food intake, body fat, insulin resistance and fatty liver compared to mice that received control bacteria.
At least four weeks after the NAPE-producing bacteria were removed from the drinking water. the protective effects persisted, with the mice still having a much lower body weight and body fat compared to the control group some 12 weeks after the NAPE-producing bacteria were removed. This is despite no active bacteria persisting after about six weeks. However, Davies says the ultimate goal is to have a one off treatment.
"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."
The approach may also provide a way to deliver to therapeutics to parts of the body outside the gut, with the team also observing effects of the NAPE compound in the liver.
"Of course it’s hard to speculate from mouse to human," added Davies. "But essentially, we’ve prevented most of the negative consequences of obesity in mice, even though they’re eating a high-fat diet."
Before it can move onto human studies, the team says it needs to address regulatory issues related to containing the bacteria, such as knocking out genes required for the bacteria to live outside the host.
The team's paper is published in the Journal of Clinical Investigation.
Source: Vanderbilt University
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