Can genetically engineered bacteria combat global obesity?
Obesity has become a world-wide epidemic that kills 2.8 million people every year. The number is rising day by day. This can also lead to certain complications like, nerve damage, renal failure, stroke, and the need for limb amputation. The main causes of obesity are: unhealthy diet, inactive lifestyle and perhaps some unlucky genes. In recent times, researchers have become more convinced that key players lie in human bowels: billions on billions of gut microbes. These vast and diverse assemblies of microbes work together, to help in regulation of 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.
FDA has not approved too many medications so that obesity and related metabolic diseases can be effectively treated.
However, a group of researchers demonstrated that genetically altered gut bacteria, are the promising candidates to prevent weight gain. These genetically modified bacteria can colonize in the gut to prevent obesity and related disorders. They modified a probiotic strain of bacteria, Escherichia coli Nissle 1917 (EcN), to express high amounts of a hormone called N-acylphosphatidylethanolamine (NAPE). 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. In fact obese people do not synthesize sufficient NAPE so they don’t have a feeling of satiation, so they eat more.
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. They 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.
One advantage of using laboratory-modified bacteria over the wild-type probiotics is that most beneficial bacteria don’t colonize the gut well. Using bacteria that are better-adapted to the gut means they’re more likely to take hold.
These modified bacteria are resistant to antibiotics, so that they can be easily grown in the lab for experiments. Though these bacteria haven’t shown any signs of being harmful, the researchers need to find an alternative before it can be used in humans. The alternative will also need to go rigorous testing to ensure that it does not pose any health risks.
The team now plans to optimize the bacteria for FDA approval and prepare for clinical trials in humans.
Incorporation of therapeutically modified bacteria into gut microbiota inhibits obesity. 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. J Clin Invest. 2014 Jun 24. pii: 72517.
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