What is already known
Tobacco smokers often develop non-alcoholic fatty liver disease (NAFLD), a range of liver conditions related to the accumulation of liver fat in people who drink little or no alcohol, which can lead to liver scarring and cancer. However, the molecular mechanisms that link tobacco smoking to NAFLD are unclear.
What this research adds
Researchers analyzed stool and blood samples from 30 smokers and 30 non-smokers and found that high levels of nicotine accumulate in the gut of smokers. Mice that had been exposed to nicotine also accumulated the chemical in their guts — a process that made them at increased risk for developing NAFLD. The team identified a bacterium, called Bacteroides xylanisolvens, that reduced gut nicotine concentrations in mice exposed to nicotine as well as the severity of NAFLD in these animals.
The findings suggest that the gut accumulation of nicotine plays a role in NAFLD progression. They also indicate that specific gut microbes are able to break down nicotine and may prevent smoking-associated diseases in humans.
Tobacco smoking is the leading cause of preventable deaths in the world, and is associated with many diseases, including non-alcoholic fatty liver disease (NAFLD) — a range of conditions that can lead to liver scarring and cancer. Now, researchers have identified a gut bacterium that is capable of breaking down nicotine and protect mice against nicotine- associated NAFLD.
The findings, published in Nature, suggest that specific gut microbes may be able to prevent smoking-related diseases in humans. They also draw a link between the accumulation of nicotine in the gut and NAFLD progression.
Scientists have known that tobacco smokers often go on to develop NAFLD, but the molecular mechanisms that link tobacco smoking to the disease are unclear. To address this question, a team of researchers led by Changtao Jiang at Peking University analyzed stool and blood samples from 30 smokers and 30 non-smokers.
The team detected high levels of nicotine in the gut of smokers. Mice that had been exposed to nicotine also accumulated the chemical in their guts. “These results indicate that nicotine levels during smoking accumulate in the intestine to a relatively large degree, which may be of pathophysiological significance,” the researchers say.
Gut levels of nicotine were higher in germ-free mice than in those colonized with gut microbes, the researchers found. This suggested that specific gut bacteria may be able to regulate nicotine levels.
To identify those microbes, the researchers scoured the mice’s microbiota for bacterial strains known to carry genes that code for nicotine-degrading enzymes. They identified one such bacterium, called Bacteroides xylanisolvens. B. xylanisolvens reduced gut nicotine concentrations in mice exposed to nicotine as well as the severity of NAFLD in these animals, the team found.
Because B. xylanisolvens is also found in the human gut, the researchers set out to investigate how their findings correlated with NAFLD progression in people. To do so, they collected data from 83 people with NAFLD, of whom 41 were smokers.
In smokers, higher B. xylanisolvens levels were correlated with lower NAFLD severity, the researchers found. “These results suggest that B. xylanisolvens-mediated nicotine degradation potentially safeguards liver function in individuals who smoke,” they say.
Although more work is needed to understand how the gut microbiota breaks down nicotine, the study reveals that the accumulation of this chemical in the gut is a risk factor for NAFLD progression in people who smoke.