Bacteria Win the Battle of the Bulge Can genetically engineered bacteria combat global obesity? Find out... Trillions of microorganisms comprise the human gut’s microbiome—a vast and diverse ensemble of microbes that work together to help regulate our metabolic, neurological, and immune systems. However, the harmony of this important microbial community is frequently threatened in people struggling with obesity, diabetes, or cardiovascular disease. Now, scientists have created genetically modified bacteria that can colonize the gut to prevent obesity and disease caused by a high-fat diet. “It has become clear that the types of bacteria that are sitting in your GI track have a fairly significant influence on your risk for obesity, so what we’re really doing is hijacking them to help us in a way that they normally wouldn’t,” said Sean Davies, Assistant Professor of Pharmacology at Vanderbilt University School of Medicine. “Essentially we’re converting the gut bacteria into a drug delivery system.” Davies’ team modified a probiotic strain of bacteria, Escherichia coli Nissle 1917 (EcN), to express high amounts of a hormone called N-acylphosphatidylethanolamine (NAPE). According to Davies, NAPE is naturally released by the small intestines when fat is being digested, and its active metabolites (N-acylethanolamides) send signals to the brain that suppress appetite. “When people are eating high fat diets or are obese, they are actually not synthesizing as much NAPE as they should be for that meal, so they don’t have a sufficient feeling of satiation,” said Davies. The team tested their NAPE-expressing bacteria by feeding high-fat diets to healthy mice while administering the bacteria in drinking water. After 8 weeks, the team noticed that mice treated with NAPE-expressing bacteria had only 50% of the body fat of mice receiving either control bacteria or standard drinking water. Davies’ team also found a sustained reduction in food intake that lasted up to 6 weeks after treatment, resulting in lower body weights for at least 12 weeks after therapy. The team now plans to optimize the bacteria for FDA approval and prepare for clinical trials in humans. “Our goal is that people would only need booster treatment with the bacteria every six weeks or so, but would still have this continuous protection from obesity,” said Davies. Reference Chen Z, Guo L, Zhang Y, L Walzem R, Pendergast JS, Printz RL, Morris LC, Matafonova E, Stien X, Kang L, Coulon D, McGuinness OP, Niswender KD, Davies SS. Incorporation of therapeutically modified bacteria into gut microbiota inhibits obesity. J Clin Invest. 2014 Jun 24. pii: 72517.
Posted on: Wed, 20 Aug 2014 04:51:01 +0000
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