Photo of Gut microbe ‘memory’ of obesity brings weight back

Gut microbe ‘memory’ of obesity brings weight back

by Juanita Bawagan News Humans & the Microbiome 08.12.2016

Weight may come and go but the gut microbiome doesn’t easily forget.

A recent paper in Nature found that the gut retains a “memory” of obesity through lasting changes in the makeup of the microbes living in the intestines. Even after weight loss, this altered microbiome makes it more likely that obesity will recur, according to the study headed by CIFAR Senior Fellow Eran Elinav (Weizmann Institute of Science).

Researchers put obese mice on a diet until they reached a lean weight, and all of their body systems — such as physical activity and food intake — returned to normal, with one notable exception.

“The only thing that remained altered was the gut microbiome. It ‘remembers’ that these mice were once obese,” says Elinav, who was in Portland, Ore. for CIFAR’s Humans & the Microbiome program meeting.

Although diet has been shown to change the gut microbiome within days, Elinav’s research demonstrates that the altered “obese” microbiome lasts for up to six months. What’s more, this microbe memory activated exaggerated weight gain when obese mice return to a high fat diet.

The study was led by Christoph Thaiss, a PhD student in Elinav’s lab in the immunology department, and pulled in researchers ranging from mathematicians to digestive specialists, including Elinav’s collaborating team headed by Prof. Eran Segal, also from the Weizmann Institute. Together, they developed unique methods to predict and control the weight gain function.

Machine learning has been a boon for microbiome research. Algorithms allow researchers to analyze hundreds of different species of bacteria that live inside the gut in ways that were previously impossible, says Elinav. In this study, algorithms successfully predicted the weight regain in 25 formerly obese mice and 25 control mice based only on the composition of their microbiome and history of obesity.

To determine the exact trigger for the weight gain, Elinav’s team narrowed their scope using genomic and metabolic tools. They identified 773 bacterial genes that were altered by a high fat diet. Of these, 189 were considered contributors, but no single gene was responsible. Instead, the microbiome as a whole appears to control the levels of two molecules that drive weight regain. These molecules, known as flavonoids, control the mice’s metabolism and energy expenditure. As the microbiome changes, these flavonoid levels drop and mice put on extra fat and cannot burn it off as quickly.

Algorithms successfully predicted the weight regain in 25 formerly obese mice and 25 control mice based only on the composition of their microbiome and history of obesity.

These animal models help frame years of human obesity research. More than 44 per cent of the world’s population is obese and 300 million adults are suffering from morbid obesity, according to the study. Many of these individuals will try to diet, but even when successful, 80 per cent will gain back the weight or surpass it within the following months.

Elinav’s lab has not developed a miracle pill for obesity, but they have found several ways to treat it in mice based on this new knowledge.
The first treatment tested was a fecal microbiome transplant. When researchers replaced the persistent gut microbiome from successfully dieting mice with that of naïve mice that were never obese, they regained weight at a normal rate.

The second and potentially more human-friendly option is supplementing drinking water with the missing flavonoids. Post-diet mice that were given a flavonoid drink every day did not put on weight as dramatically and their flavonoid levels returned to normal despite the altered microbiome. This treatment would introduce substances affected by the microbiome rather than the microbiome itself.

The microbiome memory and its affects may seem undesirable to some, but the study suggests it serves as an important “buffer.” Elinav believes microbes co-evolved with humans to preserve energy and avoid exaggerated weight fluctuations. “For millions of years, the fear was lack of nutrition, and our systems were designed to conserve energy until adequate feeding was available again. However, in the last 100 years we have been exposed to the exact opposite environmental conditions,” he says.

“The same energy buffering systems that helped us survive may now be turning against us.”

“Persistent microbiome alterations modulate the rate of post-dieting weight regain” was published in Nature Nov. 24.

Leave a Comment

Your email address will not be published.

You may use these HTML tags and attributes: <a href="" title=""> <abbr title=""> <acronym title=""> <b> <blockquote cite=""> <cite> <code> <del datetime=""> <em> <i> <q cite=""> <s> <strike> <strong>

Related Ideas

News | Humans & the Microbiome

Yeast found in the gut linked to asthma

Yeast has joined the list of gut microbes that play a role in driving diseases like asthma. In a study...

News | Profile | Humans & the Microbiome | CIFAR Azrieli Global Scholars

Following her gut instinct

How CIFAR Azrieli Global Scholar Corinne Maurice found her way into a new field Corinne Maurice had just earned a...

News | Humans & the Microbiome

Mummy DNA reveals recent history of smallpox

The 17th century Dominican Church of the Holy Spirit is one of the oldest in Vilnius, Lithuania. Tourists and parishioners...

News | Humans & the Microbiome

Gut microbe ‘memory’ of obesity brings weight back

Weight may come and go but the gut microbiome doesn’t easily forget. A recent paper in Nature found that the...

News | Humans & the Microbiome

Q & A: Let Them Eat Dirt

Improvements in hygiene and the development of antibiotics made huge improvements in health over the 20th century. But B. Brett...

News | Video | Humans & the Microbiome

Robogut: a new generation of sequencing

CIFAR Senior Fellow & Program Director Brett Finlay presents on the human microbiome at a Public Salon event organized by...