Israeli Study Shows How Quitting Smoking Makes You Fat – and What Can Be Done Against It

The research may lead to the development of treatments that will prevent weight gain after quitting smoking

Ido Efrati
Ido Efrati
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A man smoking in a bar in Germany.
A man smoking in a bar in Germany.Credit: Reuters
Ido Efrati
Ido Efrati

Changes in the composition of gut bacteria, the microbiome, and molecules they secrete are a major factor in processes that lead to obesity, say scientists from the Weizmann Institute of Science in a paper published Wednesday in the prestigious scientific journal Nature.

The research examined weight gain – generally quite steep among those who stop smoking – and the effects of quitting smoking on the gut bacteria. The findings should lead to new solutions to reducing weight gain, and not only among former smokers.

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Over a billion people around the world smoke cigarettes, and many of them avoid stopping because they fear they will gain weight. According to the researchers, the average weight gain in the period between six and 12 months after stopping smoking is 4.5 kilograms. Thirteen percent of those who stop smoking add over 10 kilos in weight in the first year.

The reasons for weight gain after stopping smoking are still not known, but the common assumption is it stems from overeating, which represents “compensating” or is a symptom of stopping smoking – but according to the scientists, previous research has already shown these things are not connected.

The Weizmann Institute lab in which the experiment was conducted.Credit: Moni Blich/Weizmann Institute

The research team was led by Leviel Fluhr, Uria Mor and Dr. Hagit Shapira from the laboratory of Prof. Eran Elinav of the immunology department at Weizmann. The scientists wanted to study the possible involvement of intestinal bacteria and the metabolites they secrete after the cessation of smoking. They discovered that stopping smoking does express itself in a change in the composition of the microbiome – and then were able to diagnose this change as the cause that leads to weight gain. In addition, they succeeded in locating the molecules secreted by the bacteria that are involved in the weight gain process – whether it is because of stopping smoking or not.

In the first stage, the scientists showed that laboratory mice that were exposed to cigarette smoke kept their weight stable, even if they ate food with lots of fats and sugar – but when their exposure to cigarette smoke was stopped – they rapidly gained weight, similar to human beings. For a different group of mice that “stopped smoking,” the cessation was accompanied by treatment with antibiotics that depleted the microbiome.

They then found that the weight gain process among this latter group was much more moderate than for the group of mice that did not receive the antibiotics. The conclusion was that nicotine and other compounds related to smoking penetrate the intestinal tract through the bloodstream and affect the composition of the microbiome and its secretions – and also as a result the metabolism of the “smoking” mice.

To find evidence for the involvement of the gut bacteria, the scientists sampled the microbiome composition in the mice at different times throughout their exposure to cigarette smoke, and after this exposure ended too. Later, they transplanted fecal bacteria taken from “sterile” mice – ones raised in a special facility and never exposed to cigarette smoke – and with a germ-free microbiome. The research found that the mice that had microbiome transplants from the “smoking” mice gained more weight than the mice who had transplanted fecal material from mice that were never exposed to cigarette smoke. The higher weight gain was seen in the mice that received fecal transplants from the mice that had just now stopped smoking. In comparison, the transplants from mice exposed to smoking and treated with antibiotics led to much more moderate weight gains.

In the next stage, the scientists mapped out the effects of smoking on the metabolites secreted by the intestinal bacteria, and identified changes in the level of secretions of two molecules, because of the exposure to smoking: A rise in the amino acid dimethyglycine (DMG), which is produced in the body from dietary choline – and which decreases when the antibiotics are given; as well as a drop in secretions of N-acetylglycine (ACG), and which rises when the antibiotics are given. They found that these molecules influence body weight even when smoking is not involved – supplemental DMG leads to a moderate increase in weight for “non-smoking” mice too; while supplemental ACG lead to a large weight loss and other improved metabolic measurements, even when given to obese mice that had never been exposed to cigarette smoke.

In the final stage of the study, the scientists examined the microbiomes of 96 people – smokers and non-smokers. They discovered clear differences between the gut bacteria of the two groups and their secretions, including those involved in the decomposition of choline – changes that reflected the findings for the mice, too.

“Through very in-depth research in this specific context of weight gain – with the cessation of smoking, we identified the materials that are secreted by the bacteria and contribute to weight gain or weight loss,” said Elinav. “Later, we discovered that they are effective in the treatment of other types of weight gain that are not related to the cessation of smoking. The minute we crack the exact mechanism through which the bacteria contribute to weight gain, it will be possible to use in it a broader context.”

“Our findings exemplify how the host and microbiome act as partners in regulating weight and metabolism,” said Elinav, who headed the research team. “The compounds we have identified may lead to new treatments that will help people avoid weight gain when quitting smoking. Moreover, these compounds may be further developed into therapies to fight obesity even among non-smokers.”

“The profound impact that our microbial tenants have on our body never ceases to amaze us,” Elinav said. “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.”

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