Sun Jinchun, Jin Jinshan, Beger Richard D, Cerniglia Carl E, Yang Maocheng, Chen Huizhong
Division of Systems Biology, National Center for Toxicological Research, US FDA, 3900 NCTR Rd, Jefferson, AR 72079, United States.
Division of Microbiology, National Center for Toxicological Research, US FDA, 3900 NCTR Rd, Jefferson, AR 72079, United States.
Toxicol In Vitro. 2016 Oct;36:133-141. doi: 10.1016/j.tiv.2016.07.020. Epub 2016 Jul 30.
The association between exposure to smokeless tobacco products (STP) and oral diseases is partially due to the physiological and pathological changes in the composition of the oral microbiome and its metabolic profile. However, it is not clear how STPs affect the physiology and ecology of oral microbiota. A UPLC/QTof-MS-based metabolomics study was employed to analyze metabolic alterations in oral bacterium, Capnocytophaga sputigena as a result of smokeless tobacco exposure and to assess the capability of the bacterium to metabolize nicotine. Pathway analysis of the metabolome profiles indicated that smokeless tobacco extracts caused oxidative stress in the bacterium. The metabolomics data also showed that the arginine-nitric oxide pathway was perturbed by the smokeless tobacco treatment. Results also showed that LC/MS was useful in identifying STP constituents and additives, including caffeine and many flavoring compounds. No significant changes in levels of nicotine and its major metabolites were found when C. sputigena was cultured in a nutrient rich medium, although hydroxylnicotine and cotinine N-oxide were detected in the bacterial metabolites suggesting that nicotine metabolism might be present as a minor degradation pathway in the bacterium. Study results provide new insights regarding the physiological and toxicological effects of smokeless tobacco on oral bacterium C. sputigena and associated oral health as well as measuring the ability of the oral bacterium to metabolize nicotine.
接触无烟烟草制品（STP）与口腔疾病之间的关联部分归因于口腔微生物群组成及其代谢谱的生理和病理变化。然而，尚不清楚STP如何影响口腔微生物群的生理学和生态学。采用基于超高效液相色谱/四极杆飞行时间质谱（UPLC/QTof-MS）的代谢组学研究来分析因接触无烟烟草而导致的口腔细菌——生痰二氧化碳嗜纤维菌的代谢变化，并评估该细菌代谢尼古丁的能力。代谢组图谱的通路分析表明，无烟烟草提取物会在细菌中引起氧化应激。代谢组学数据还显示，无烟烟草处理会扰乱精氨酸-一氧化氮途径。结果还表明，液相色谱/质谱（LC/MS）有助于识别STP成分和添加剂，包括咖啡因和许多调味化合物。当生痰二氧化碳嗜纤维菌在营养丰富的培养基中培养时，未发现尼古丁及其主要代谢物水平有显著变化，尽管在细菌代谢物中检测到了羟基尼古丁和可替宁N-氧化物，这表明尼古丁代谢可能是该细菌中的一条次要降解途径。研究结果为无烟烟草对口腔细菌生痰二氧化碳嗜纤维菌的生理和毒理学影响以及相关口腔健康提供了新的见解，同时也测定了口腔细菌代谢尼古丁的能力。
