A gut microbe has been discovered that can break down nicotine and, if abundant enough, may reduce harm to smokers, reports a Sino-American collaboration. This finding might one day translate into a therapy that saves lives.
The work began with a clinical trial in China that found an ‘unexpected’ accumulation of nicotine in the gut, with nicotine and its metabolites detected in human stool samples, says Frank Gonzalez at the National Cancer Institute in Bethesda, Maryland. A screen of stool samples from smokers and non-smokers then led to the identification of a bacterium that degraded nicotine. The bacterium, Bacterioides xylanisolvens, was demonstrated to break down nicotine in culture.
This led the researchers to wonder if this bacterium might protect against non-alcoholic fatty liver disease (NAFLD), a condition linked to smoking. Mice given nicotine and then inoculated with B. xylanisolvens showed slower progression of this disease.
A study of 41 smokers and 42 non-smokers in China subsequently revealed that levels of B. xylanisolvens were correlated with NAFLD severity. Faecal nicotine levels were higher in those with NAFLD, suggesting that smokers with lower levels of this bacterium had more nicotine in their gut. ‘The bacteria leads to a difference between low nicotine levels and high nicotine levels [in the intestine] in smokers,’ says Lulu Sun, a postdoc researcher at the National Cancer Institute.
‘Tobacco smoking exposes the heart, lungs and internal organs to nicotine and other poisonous compounds, but no one had expected a direct link between tobacco smoking and liver disease,’ says Gonzalez. NAFLD is also linked to increased risk of liver cancer. Gonzalez expressed surprise that a gut bacterial enzyme could be involved in reducing harm caused by nicotine.
His lab has investigated mechanisms of extreme NAFLD, whereby the liver becomes inflamed, leading to non-alcoholic steatohepatitis. The latest study found that nicotine activates the enzyme AMPK in the gut of mice, which stabilises another enzyme, resulting in a build-up of ceramide lipids.
Earlier studies showed ‘quite convincingly in the mouse that ceramide produced in the intestines leads to metabolic disease’, says Gonzalez, ‘and elevated serum ceramide levels have been correlated with increases in fatty liver disease, diabetes and obesity’.
The findings could be turned into a therapy. Sun says that his collaborators in China are focusing on the microbiome and investigating whether the bacterium could be given as a probiotic. B. xylanisolvens has been shown to be safe, and the EU has authorised its inclusion in milk products. It is currently unclear if certain dietary choices or lifestyle factors affect its abundance.
‘It is not too surprising that a gut-related bacteria can degrade nicotine, but the findings overall are quite thought provoking,’ says Kim Janda, chemical biologist at Scripps Research in La Jolla, California. He would like to know how long nicotine tends to stay in the gut of smokers before being metabolised, and whether B. xylanisolvens numbers spike after an individual smokes. ‘There are billions of bacteria that colonise our intestines and I am sure that this is not the only one that is contributing to nicotine degradation,’ Janda adds.
B Chen et al, Nature, 2022, DOI: 10.1038/s41586-022-05299-4