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Experiments With Mice Show When Weight Is Lost, the Gut Remembers


The phenomenon of "yo-yo" dieting has health consequences and frustrates dieters themselves. Studies show each round of weight loss and weight regain produces harsher metabolic effects.

New research in mice may explain why people who lose weight have such a hard time keeping it off: microbes in the intestines, known as the gut microbiome, retain a “memory” of obesity against the body’s efforts to function in its newly slender state.

The findings, published in the journal Nature, explain the phenomenon of “yo-yo” dieting, and why some people repeatedly lose weight only to regain it. For many, they not only regain the weight lost but even more, all the while acquiring more characteristics of metabolic disease.

Led by Eran Elinav, MD, PhD, an immunologist, and Eran Segal, PhD, a computational biologist, both of the Weizmann Institute of Science, the research team found that after gaining and losing weight, all the body systems in the mice returned to normal—with the exception of the gut microbiome. This system retained its “obese” characteristics for at least 6 months after weight loss.

“The microbiome retains a memory of previous obesity,” Elinav said. This means that as soon as the mice returned to eating a normal diet, the microbiome sped up the body’s process of regaining weight. But the good news, Elinav said, is that the researchers have closely examined how the microbiome functions, which could lead to the development of treatments to prevent successful dieters from regaining weight.

The phenomenon of recurrent obesity, and the body’s stubborn ability to regain the weight that people struggle so hard to lose, has been the subject of multiple studies and countless New Year’s resolutions. A well-publicized study was published in May 2016, after scientists at the National Institutes of Health spent 6 years monitoring contestants from the 2009 season of “The Biggest Loser.” The majority of the 16 contestants regained most, if not all, of their weight, and some were even heavier. One researcher marveled at the body’s persistence to regain weight, calling it “frightening and amazing.”

In this new study, the Weizmann scientists performed a series of experiments with mice to understand the microbiome’s role. They depleted intestinal microbes by giving the mice antibiotics, which drowned out the post-diet weight gain. When mice with an obesity history were introduced to germ-free mice—who have no microbiome—the germ-free mice rapidly gained weight from the high-calorie diet, much faster than germ-free mice implanted with microbiomes from mice with a normal weight history.

The team developed an algorithm that accurately predicted which mice would regain weight and how quickly, and they also performed a proof-of-concept experiment, which showed that transplanting a microbiome in obese mice could wipe out the “memory” driving the weight gain. This could lay the groundwork for a successful treatment for patients with recurrent weight gain, which has both harmful health effects and discouraging mental health burdens.


Thais CA, Itav S, Rothschild D, et al. Persistent microbiome alterations modulate the rate of post-dieting weight regain. Nature. 2016; DOI: 10.1038/nature20796

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