Weight gain following quitting smoking is such a common phenomenon it is often cited as one of the main reasons people are hesitant to quit. A new mouse study published in the journal Nature has homed in on a potential role the gut microbiome may play in influencing weight gain associated with the cessation of smoking.
Although the phenomenon of weight gain after quitting smoking is well known, the actual mechanisms at play are not clear. Researchers have long speculated a variety of metabolic and genetic reasons likely influence weight gain after quitting smoking, including changes to appetite stimulation previously modified by nicotine.
Across a series of clever mouse experiments new research demonstrates the role gut bacteria may play in weight gain following quitting smoking. The study first found mice exposed to cigarette smoke resisted weight gain when fed a diet high in fat, but when the smoke exposure was halted the animals subsequently gained weight.
The researchers then used antibiotics to deplete the animals’ gut microbiome and observed less weight gain after stopping smoke exposure compared to animals with a regular microbiome. To further confirm the role of gut bacteria in the weight gain the researchers performed fecal transplants from smoke-exposed mice to normal mice.
Across two different cohorts of mice on two different diets the researchers constantly saw the animals gain weight when transplanted with the microbiota of smoke-exposed mice. This suggested gut bacteria may be playing a role in smoking-associated weight gain.
The next step in the research was to home in on what specific gut bacteria metabolites were influenced by cigarette smoke and could potentially be playing a role in these weight changes. Two particular gut bacteria metabolites stood out to the researchers: dimethylglycine (DMG) and acetylglycine (ACG).
DMG levels were enhanced and ACG levels were reduced in mice exposed to cigarette smoke. The researchers discovered weight gain in the mice no longer exposed to cigarette smoke could be stopped by either inhibiting DMG metabolism or supplementing ACG.
Even more interestingly, the researchers found weight gain could be influenced in mice not exposed to smoke by modulating levels of these metabolites. Healthy mice given DMG supplements displayed modest weight gain and healthy mice given ACG supplements lost weight.
The last step in the study was to investigate this phenomenon in humans. The researchers studied the microbiomes of 96 subjects and found smokers displayed similar metabolite profiles to what was seen in the smoke-exposed mice. In particular, the study notes human smokers showed distinct increases in DMG levels.
“The profound impact that our microbial tenants have on our body never ceases to amaze us,” says Erin Elinav, a researcher working on the study. “Our findings shed new light on how the microbiome interacts with the human body in regulating our weight and metabolism, in ways that may be therapeutically exploited.”
Of course, a lot more work is needed to translate these results across to human subjects but the findings offer compelling clues as to how smoking can remodel gut bacteria populations in ways that broadly influence metabolism. Elinav speculates the findings could inform more general anti-obesity therapies beyond simply helping reduce weight gain in smokers trying to quit.
“The compounds we have identified may lead to new treatments that will help people avoid weight gain when quitting smoking,” Elinav says. “Moreover, these compounds may be further developed into therapies to fight obesity even among nonsmokers.”
The new study was published in the journal Nature.
Source: Weizmann Institute of Science
