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Gut bacteria alleviate smoking-related NASH by degrading gut nicotine
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Journal Article
Gut bacteria alleviate smoking-related NASH by degrading gut nicotine
2022
Overview
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.
Nicotine accumulates in the intestine during tobacco smoking and accelerates the progression of non-alcoholic fatty liver disease to non-alcoholic steatohepatitis (NASH), but it can be degraded effectively by the human symbiont
Bacteroides xylanisolvens.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ AMP-Activated Protein Kinases - metabolism
/ Animals
/ Bacteria
/ Biopsy
/ Ceramide
/ E coli
/ Genes
/ Humanities and Social Sciences
/ Humans
/ Liver
/ Mice
/ Nicotine
/ NMR
/ Non-alcoholic Fatty Liver Disease - chemically induced
/ Non-alcoholic Fatty Liver Disease - etiology
/ Non-alcoholic Fatty Liver Disease - microbiology
/ Science
/ Smoking
/ Sphingomyelin phosphodiesterase
/ Sphingomyelin Phosphodiesterase - metabolism
/ Tobacco
