Abstract

Tobacco smoking is positively correlated with non-alcoholic fatty liver disease (NAFLD)1-5, but the underlying mechanism for this association is unclear. Here we report that nicotine accumulates in the intestine during tobacco smoking and activates intestinal AMPKα. We identify the gut bacterium Bacteroides xylanisolvens as an effective nicotine degrader. Colonization of B. xylanisolvens reduces intestinal nicotine concentrations in nicotine-exposed mice, and it improves nicotine-exacerbated NAFLD progression. Mechanistically, AMPKα promotes the phosphorylation of sphingomyelin phosphodiesterase 3 (SMPD3), stabilizing the latter and therefore increasing intestinal ceramide formation, which contributes to NAFLD progression to non-alcoholic steatohepatitis (NASH). Our results establish a role for intestinal nicotine accumulation in NAFLD progression and reveal an endogenous bacterium in the human intestine with the ability to metabolize nicotine. These findings suggest a possible route to reduce tobacco smoking-exacerbated NAFLD progression.

Smoking has been linked to non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease is a condition where excessive fat is stored in the liver of non-alcoholic drinkers.[1]

Some people with non-alcoholic fatty liver disease can develop steatohepatitis, an aggressive form of fatty liver disease, which may progress to cirrhosis and liver failure.[1]

Researchers discovered that nicotine may accumulate in the intestine of a smoker and activates intestinal AMPKα.

Researchers found that the bacterium Bacteroides xylanisolvens can degrade intestinal nicotine in mice.

Additionally, AMPKα was found to increase intestinal ceramide formation which helps the progression of non-alcoholic fatty liver disease into steatohepatits.

The results highlight the effect of intestinal nicotine accumulation and the discovery of a bacterium that can eliminate intestinal nicotine which reduces liver disease.

Sources:

Chen, B., Sun, L., Zeng, G., Shen, Z., Wang, K., Yin, L., Xu, F., Wang, P., Ding, Y., Nie, Q., Wu, Q., Zhang, Z., Xia, J., Lin, J., Luo, Y., Cai, J., Krausz, K. W., Zheng, R., Xue, Y., Zheng, M. H., … Jiang, C. (2022). Gut bacteria alleviate smoking-related NASH by degrading gut nicotine. Nature, 610(7932), 562–568. https://doi.org/10.1038/s41586-022-05299-4

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