Chi Liang, Mahbub Ridwan, Gao Bei, Bian Xiaoming, Tu Pengcheng, Ru Hongyu, Lu Kun
Department of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina 27599, United States.
Department of Environmental Health Science, University of Georgia , Athens, Georgia 30602, United States.
Chem Res Toxicol. 2017 Dec 18;30(12):2110-2119. doi: 10.1021/acs.chemrestox.7b00162. Epub 2017 Nov 16.
As the primary active substance in tobacco, nicotine affects the activity of the central nervous system, and its effects are sex-dependent. There are complex interactions between the gut and brain, and the gut microbiome can influence neuronal activity and host behavior, with diverse chemical signaling being involved. However, it is unclear whether nicotine can affect the normal gut microbiome and associated chemical signaling of the gut-brain axis. Sex is an important factor that shapes the gut microbiome, but the role of sex in the interaction among nicotine, gut bacteria, and related metabolites remains unknown. In this study, we applied high-throughput sequencing and gas chromatography-mass spectrometry (GC-MS) to explore how nicotine exposure affects the gut microbiome and its metabolism in female and male C57BL/6J mice, with a focus on the chemical signaling involved in gut-brain interactions. 16S sequencing results indicated that the community composition of the gut microbiome was differentially perturbed by nicotine in females and males. Differential alterations of bacterial carbohydrate metabolic pathways are consistent with lower body weight gain in nicotine-treated males. Oxidative stress response and DNA repair genes were also specifically enriched in the nicotine-treated male gut microbiome. The fecal metabolome indicated that multiple neurotransmitters, such as glutamate, gamma-aminobutyric acid (GABA), and glycine, were differentially altered in female and male mice. Some neuroactive metabolites, including leucine and uric acid, were also changed. This study demonstrates a sex-dependent effect of nicotine on gut microbiome community composition, functional bacterial genes, and the fecal metabolome.
作为烟草中的主要活性物质，尼古丁会影响中枢神经系统的活动，且其作用存在性别差异。肠道与大脑之间存在复杂的相互作用，肠道微生物群可影响神经元活动和宿主行为，其中涉及多种化学信号传导。然而，尚不清楚尼古丁是否会影响正常的肠道微生物群以及肠-脑轴相关的化学信号传导。性别是塑造肠道微生物群的一个重要因素，但性别在尼古丁、肠道细菌及相关代谢产物相互作用中的作用仍不清楚。在本研究中，我们应用高通量测序和气相色谱-质谱联用技术（GC-MS），来探究尼古丁暴露如何影响雌性和雄性C57BL/6J小鼠的肠道微生物群及其代谢，重点关注肠-脑相互作用中涉及的化学信号传导。16S测序结果表明，雌性和雄性小鼠的肠道微生物群落组成因尼古丁而受到不同程度的扰动。细菌碳水化合物代谢途径的差异改变与尼古丁处理的雄性小鼠体重增加较低一致。氧化应激反应和DNA修复基因也在尼古丁处理的雄性小鼠肠道微生物群中特异性富集。粪便代谢组学表明，雌性和雄性小鼠中多种神经递质，如谷氨酸、γ-氨基丁酸（GABA）和甘氨酸，发生了不同程度的改变。一些神经活性代谢产物，包括亮氨酸和尿酸，也发生了变化。本研究证明了尼古丁对肠道微生物群落组成、功能性细菌基因和粪便代谢组具有性别依赖性影响。
