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GI highlights from the literature
  1. Philip J Smith
  1. Department of Gastroenterology, Royal Liverpool Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
  1. Correspondence to Dr Philip J Smith, Department of Gastroenterology, Royal Liverpool Hospital, Liverpool University Hospitals NHS Foundation Trust, Liverpool, L7 8XP, UK; drphilipjsmithbsg{at}gmail.com

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Basic science

Gut microbiome-mediated nicotine degradation protects against smoking-related non-alcoholic fatty liver disease (NAFLD)

Chen B, Sun L, Zeng G, et al. Gut bacteria alleviate smoking-related NASH by degrading gut nicotine. Nature 2022; 610: 562-568, doi: 10.1038/s41586-022-05299-4.

Tobacco smoking is associated with NAFLD, with nicotine in particular contributing adversely towards this association; however, mechanistic understanding of this process is lacking. This study by Chen et al explored the possible contribution of a microbiome-related pathway.

Investigators observed nicotine accumulation particularly in the ileum of tobacco smokers. Nicotine-exposed germ-free (GF) mice developed greater ileal nicotine accumulation than conventional mice, suggesting gut microbiome-mediated nicotine degradation. Metagenomic analysis of smokers identified Bacteroides xylanisolvens as a gut bacterium with potential nicotine catabolic functionality.

Colonisation of mice with B. xylanisolvens confirmed this bacterium’s ability to degrade nicotine in vivo. Experiments involving introduction of the nicX gene into Escherichia coli or its knockout from B. xylanisolvens confirmed this bacterium’s NicX protein as a nicotine catabolic enzyme.

High-fructose high-cholesterol diet mice were used as a model of NAFLD, with mice provided either standard or nicotine-supplemented water and colonised with either wild-type (WT) or nic-X knockout B. xylanisolvens. Mice exposed to nicotine developed accelerated NAFLD; this was mitigated in mice colonised with WT (but not nic-X knockout) B. xylanisolvens. In addition, AMP-activated protein kinase alpha was shown to contribute to phosphorylation of sphingomyelin phosphodiesterase 3, with the stabilisation associated with this contributing to increased intestinal ceramide generation, and associated NAFLD progression through to non-alcoholic steatohepatitis.

Finally, investigators demonstrated that gut B. xylanisolvens levels were negatively associated with NAFLD severity in smokers with NAFLD; conversely, faecal nicotine levels correlated positively with NAFLD severity.

Collectively, this work gives further insight into the interaction between smoking, the gut microbiome, altered intestinal metabolites and NAFLD progression.

Activation of hepatic stellate cells (HSCs) in liver fibrosis promotes hepatocellular carcinoma (HCC) development

Filliol A, Saito Y, Nair A, et al. Opposing roles of hepatic stellate cell subpopulations in hepatocarcinogenesis. …

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Footnotes

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.