德国魏茨曼科学研究所Eran Elinav和Hagit Shapiro研究小组合作取得一项新突破。他们研究发现停止吸烟后，肠道菌群调节小鼠体重增加。该项研究成果发表在2021年12月8日出版的《自然》上。

研究人员使用小鼠模型来证明吸烟和戒烟会诱发一种由肠道内与香烟相关的代谢物流入失调状态。利用抗生素消除肠道微生物组可防止戒烟引起的体重增加（SCWG）。相反，将先前接触过香烟烟雾小鼠的粪便微生物组移植到未接触过烟雾的无菌小鼠会导致小鼠饮食和体重过度增加。在代谢方面，微生物组诱导的SCWG会诱发宿主和微生物组将膳食胆碱分流至二甲基甘氨酸，从而增加肠道能量收集，同时消耗交叉调节的减重代谢物N-乙酰甘氨酸，可能还受其他与香烟烟雾相关代谢物丰度的影响。

在非吸烟条件下，二甲基甘氨酸和N-乙酰甘氨酸还可以调节体重和相关的脂肪组织免疫。在少量人群实验中的初步观察支持这些发现，但还需要更大规模的人体试验来确定这种机制在主动吸烟者中的相关性。总的来说，该研究揭示了一个微生物组依赖的SCWG机制，即使在非吸烟环境中，它也可用于提高戒烟成功率和调控代谢紊乱。

据悉，吸烟是造成全球死亡率上升的主要原因，大多数长期吸烟表示有戒烟的愿望或最近尝试戒烟。SCWG（据报道平均每 6-12个月增加4.5公斤，13%的戒烟者平均每年增加10公斤）是戒烟的主要障碍，即使在稳定或限制热量摄入的情况下依然会发生。

附：英文原文

Title: Gut microbiota modulates weight gain in mice after discontinued smoke exposure

Author: Fluhr, Leviel, Mor, Uria, Kolodziejczyk, Aleksandra A., Dori-Bachash, Mally, Leshem, Avner, Itav, Shlomik, Cohen, Yotam, Suez, Jotham, Zmora, Niv, Moresi, Claudia, Molina, Shahar, Ayalon, Niv, Valds-Mas, Rafael, Hornstein, Shanni, Karbi, Hodaya, Kviatcovsky, Denise, Livne, Adi, Bukimer, Aurelie, Eliyahu-Miller, Shimrit, Metz, Alona, Brandis, Alexander, Mehlman, Tevie, Kuperman, Yael, Tsoory, Michael, Stettner, Noa, Harmelin, Alon, Shapiro, Hagit, Elinav, Eran

Issue&Volume: 2021-12-08

Abstract: Cigarette smoking constitutes a leading global cause of morbidity and preventable death1, and most active smokers report a desire or recent attempt to quit2. Smoking-cessation-induced weight gain (SCWG; 4.5kg reported to be gained on average per 6–12months, >10kgyear–1 in 13% of those who stopped smoking3) constitutes a major obstacle to smoking abstinence4, even under stable5,6 or restricted7 caloric intake. Here we use a mouse model to demonstrate that smoking and cessation induce a dysbiotic state that is driven by an intestinal influx of cigarette-smoke-related metabolites. Microbiome depletion induced by treatment with antibiotics prevents SCWG. Conversely, fecal microbiome transplantation from mice previously exposed to cigarette smoke into germ-free mice naive to smoke exposure induces excessive weight gain across diets and mouse strains. Metabolically, microbiome-induced SCWG involves a concerted host and microbiome shunting of dietary choline to dimethylglycine driving increased gut energy harvest, coupled with the depletion of a cross-regulated weight-lowering metabolite, N-acetylglycine, and possibly by the effects of other differentially abundant cigarette-smoke-related metabolites. Dimethylglycine and N-acetylglycine may also modulate weight and associated adipose-tissue immunity under non-smoking conditions. Preliminary observations in a small cross-sectional human cohort support these findings, which calls for larger human trials to establish the relevance of this mechanism in active smokers. Collectively, we uncover a microbiome-dependent orchestration of SCWG that may be exploitable to improve smoking-cessation success and to correct metabolic perturbations even in non-smoking settings.

DOI: 10.1038/s41586-021-04194-8

Source: https://www.nature.com/articles/s41586-021-04194-8