For those who have lost the same 10, 20 or 50 pounds not once but many times over, new research may help explain why yo-yo dieters so often fail to maintain their hard-won weight loss.

The community of microorganisms that inhabit the gut are a key culprit, experiments in mice suggest. After being altered by obesity, this collection of bacteria, viruses and protozoa — collectively known as the gut microbiome — subverts any effort to keep lost weight off. Instead, it seems to encourage the body to regain lost weight by storing more calories as fat, and it does so in ways that exaggerate the body’s unhealthy metabolic response to weight gain.

The findings, published Thursday in the journal Nature, offer fresh insight into a problem that dieters know too well: As many as 95% of those who lose at least a tenth of their body weight tend to gain it back within a year, along with a little extra.

But the research also offers hope that this problem may be overcome by giving the gut a little boost.


“Diets generally fail and don’t work, but not because they don’t work initially,” said computational biologist Eran Segal of the Weizmann Institute of Science in Israel, one of the study’s senior authors. “The problem is the weight regain.”

Humans and the microbes that colonize their guts probably evolved together in ways that helped people weather famine and other forms of dietary deprivation, Segal said. But in a world where calories are cheap, plentiful and ubiquitous, our gut microbiomes are “now acting against us.”

For the study, researchers cycled mice between diets of high-fat chow, which made them obese, and normal chow, which caused them to lose weight. However, when they went back on the high-fat chow, they often gained a little more weight than they had before.

Indeed, yo-yo dieting made for mice that were distinctly less healthy than mice who had been fat just once. The serial dieters had higher proportions of body fat, more worrisome cholesterol profiles, and more serious metabolic problems, such as insulin irregularities and glucose intolerance, the study authors reported.


How could this be?

The researchers found that it took a little over a month for a mouse to lose weight by going on a diet. But it took six months — a quarter of a mouse’s average lifespan — for the composition of the gut microbiome to revert to its healthy, pre-obesity state.

In a series of experiments, the researchers demonstrated that the gut microbiome of an obese mouse becomes deficient in its ability to respond to plant compounds called flavonoids.

The resulting suppression of flavonoid levels has a very specific effect on the body’s energy-burning system: It makes brown fat, which acts as a high-intensity furnace for converting calories to energy, more efficient.


As a result, the body uses incoming calories more sparingly and stores anything left over as fat. That means that after they’ve dieted away their excess weight, once-chubby mice who return to a high-fat diet will quickly regain that weight, and more.

Using their newfound insights, however, the researchers tried a relatively easy fix. During the post-dieting window before their gut microbiomes had returned to normal, the researchers gave some of the mice daily flavonoid supplements.

Compared with yo-yo dieters who got no such supplements, those that got the daily flavonoids burned up more calories when they returned to a high-fat diet. They also regained less weight.

It’s “a common problem — namely, failure to maintain weight loss,” said Dr. Lawrence J. Brandt, a gastroenterologist from Albert Einstein College of Medicine in New York City, who wasn’t involved in the research. Anything that sheds light on this difficult dynamic would be exciting, he said.


The new research points to the potential value of a practice coming into more widespread use: restoring a person’s lost or missing gut microbes with a transplant of intestinal flora from a healthy donor.

Such transplants, effected by the transfer of treated fecal matter, have cleared up stubborn intestinal diseases, such as chronic Clostridium difficile infection. Some scientists hold out hope that fecal transplants from lean people to those whose gut microbiomes have been altered by obesity might help people lose weight, keep it off and ward off diseases of obesity like Type 2 diabetes.

The medical community already has some evidence that this might work, albeit in reverse.

In 2015, doctors reported the case of a 136-pound woman who quickly gained more than 40 pounds after receiving a fecal transplant from her overweight daughter. The mother was being treated for a C. diff infection that kept coming back despite five rounds of antibiotics.


The fecal transplant cured her infection.

melissa.healy@latimes.com

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