Scientific publications
Gut microbiota modulates weight gain in mice after discontinued smoke exposure
Leviel Fluhr # 1, Uria Mor # 1, Aleksandra A Kolodziejczyk 1, Mally Dori-Bachash 1, Avner Leshem 1 2, Shlomik Itav 1, Yotam Cohen 1, Jotham Suez 1, Niv Zmora 1 3 4, Claudia Moresi 1, Shahar Molina 1, Niv Ayalon 1, Rafael Valdés-Mas 1, Shanni Hornstein 1, Hodaya Karbi 1, Denise Kviatcovsky 1, Adi Livne 1, Aurelie Bukimer 1, Shimrit Eliyahu-Miller 1, Alona Metz 1, Alexander Brandis 5, Tevie Mehlman 5, Yael Kuperman 6, Michael Tsoory 6, Noa Stettner 6, Alon Harmelin 6, Hagit Shapiro 7, Eran Elinav 8 9
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; 4.5 kg reported to be gained on average per 6-12 months, >10 kg year-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.
CITA DEL ARTÍCULO Nature. 2021 Dec;600(7890):713-719. doi: 10.1038/s41586-021-04194-8. Epub 2021 Dec 8.
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