小柯机器人

北京大学姜长涛等研究人员合作发现，肠道细菌通过降解肠道尼古丁缓解吸烟相关的NASH。这一研究成果于2022年10月19日发表在国际学术期刊《自然》上。

研究人员发现，尼古丁在吸烟期间会在肠道内累积，并激活肠道AMPKα。结果表明，肠道细菌Bacteroides xylanisolvens是一种有效的尼古丁降解剂。B. xylanisolvens的定植可以降低暴露于尼古丁的小鼠肠道尼古丁浓度，并且可以改善尼古丁加重的非酒精性脂肪肝的进展。从机制上讲，AMPKα促进了鞘磷脂磷酸二酯酶3（SMPD3）的磷酸化，稳定了后者，从而增加了肠道神经酰胺的形成，这有助于非酒精性脂肪肝向非酒精性脂肪肝炎（NASH）发展。

这些研究结果确立了肠道尼古丁积累在非酒精性脂肪肝进展中的作用，并揭示了人类肠道中一种具有代谢尼古丁能力的内源性细菌。这些发现为减少吸烟加剧的非酒精性脂肪肝的进展提供了可能的途径。

据悉，吸烟与非酒精性脂肪肝（NAFLD）呈正相关，但这种关联的潜在机制尚不清楚。

附：英文原文

Title: Gut bacteria alleviate smoking-related NASH by degrading gut nicotine

Author: Chen, Bo, Sun, Lulu, Zeng, Guangyi, Shen, Zhe, Wang, Kai, Yin, Limin, Xu, Feng, Wang, Pengcheng, Ding, Yong, Nie, Qixing, Wu, Qing, Zhang, Zhiwei, Xia, Jialin, Lin, Jun, Luo, Yuhong, Cai, Jie, Krausz, Kristopher W., Zheng, Ruimao, Xue, Yanxue, Zheng, Ming-Hua, Li, Yang, Yu, Chaohui, Gonzalez, Frank J., Jiang, Changtao

Issue&Volume: 2022-10-19

Abstract: Tobacco smoking is positively correlated with non-alcoholic fatty liver disease (NAFLD)1,2,3,4,5, 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.

DOI: 10.1038/s41586-022-05299-4

Source: https://www.nature.com/articles/s41586-022-05299-4

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