Genetically Modified Bacteria Enable Weight Loss In Mice and could work in humans better than drugs to blunt the obesity epidemic

Mice given genetically-tweaked E. coli in their water gained less weight than controls when placed on a high-fat diet for 8 weeks. They also had fewer markers of diabetes, like insulin resistance, and generally ate less than their compatriots receiving nothing or control bacteria. And for 4 weeks to 6 weeks after the researchers stopped dosing the water, the beneficial effects persisted.

The bacteria given to the mice were genetically engineered to express predecessors of a family of fats that prompt less food intake. These fats are made in the small intestine, and tell an animal to stop eating. High fat diets interfere with this process, so using modified bacteria may help dieters regulate their appetites.

Journal of Clinical Investigation – Incorporation of therapeutically modified bacteria into gut microbiota inhibits obesity

First, the scientists picked a strain to target: a type of E. coli. Then they altered the strain to add a gene found in arabidopsis, the first plant to have its genome sequenced.

The gene prompts the bacteria to make precursors to the hormones released in the small intestine when it processes fat. These hormones, dubbed NAE, travel through the bloodstream to the brain to suppress appetite. The bacteria release these hormones in the gut of the mice who ingested them, without any apparent ill-effects for their hosts. As for how they ate: they ate normally timed meals, just smaller ones than the control mice. They also seemed to move more, including during the light phase of their day, when mice are generally asleep.

More than a third of adults in the U.S. are obese, and the condition has been notoriously difficult to target with drugs. Wyeth, which was subsequently bought by Pfizer, had some successes with fenfluramine and dexflenfluramine before the drugs were pulled from the market in 1997, when they were linked to heart valve disease in patients who took them with phentermine. Sanofi stopped developing its obesity treatment Accomplia in the U.S. after Europeans removed it from the market for its links to suicide and depression. Pfizer and Merck both stopped development on obesity programs in 2008. Abbott Laboratories’ diet pill Meridia was similarly yanked from the market in 2010 for its links to heart attacks and strokes.

Unlike these drugs, which need to be taken daily, today’s results suggest bacteria can be dosed as infrequently as once every 4 weeks, while retaining their beneficial effects, the researchers wrote. And the effect of the hormonal precursors is both limited and specific: there weren’t any significant elevations of NAE in the blood of the mice — just in the liver and the brain

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