Gut bacteria alleviate smoking-related NASH by degrading gut nicotine

Nature. 2022 Oct;610(7932):562-568. doi: 10.1038/s41586-022-05299-4. Epub 2022 Oct 19.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Bacteria* / drug effects
  • Bacteria* / metabolism
  • Ceramides / biosynthesis
  • Disease Progression
  • Humans
  • Intestines* / drug effects
  • Intestines* / microbiology
  • Mice
  • Nicotine* / adverse effects
  • Nicotine* / metabolism
  • Non-alcoholic Fatty Liver Disease* / chemically induced
  • Non-alcoholic Fatty Liver Disease* / etiology
  • Non-alcoholic Fatty Liver Disease* / microbiology
  • Sphingomyelin Phosphodiesterase / metabolism
  • Tobacco Smoking* / adverse effects
  • Tobacco Smoking* / metabolism


  • Ceramides
  • Nicotine
  • Smpd3 protein, mouse
  • Sphingomyelin Phosphodiesterase
  • AMP-Activated Protein Kinases

Supplementary concepts

  • Bacteroides xylanisolvens