| Literature DB >> 36261549 |
Bo Chen1,2,3,4, Lulu Sun5, Guangyi Zeng1,2,3,4, Zhe Shen6, Kai Wang1,2,3,4, Limin Yin7, Feng Xu1,2,3,4, Pengcheng Wang1,2,3,4, Yong Ding1,2,3,4, Qixing Nie1,2,3,4, Qing Wu1,2,3,4, Zhiwei Zhang1,2,3,4, Jialin Xia1,2,3,4, Jun Lin1,2,3,4, Yuhong Luo5, Jie Cai5, Kristopher W Krausz5, Ruimao Zheng8, Yanxue Xue9, Ming-Hua Zheng10,11, Yang Li12, Chaohui Yu13, Frank J Gonzalez14, Changtao Jiang15,16,17,18.
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.Entities:
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Year: 2022 PMID： 36261549 DOI： 10.1038/s41586-022-05299-4
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 69.504