title: Metabolomics evaluation of the impact of smokeless tobacco exposure on the oral bacterium Capnocytophaga sputigena.
abstract: 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.
authors.affiliation: Division of Systems Biology, National Center for Toxicological Research, US FDA, 3900 NCTR Rd, Jefferson, AR 72079, United States. Electronic address: Jinchun.Sun@fda.hhs.gov.
authors.forename: Jinchun
authors.initials: J
authors.lastname: Sun
authors.affiliation: Division of Microbiology, National Center for Toxicological Research, US FDA, 3900 NCTR Rd, Jefferson, AR 72079, United States.
authors.forename: Jinshan
authors.initials: J
authors.lastname: Jin
authors.affiliation: Division of Systems Biology, National Center for Toxicological Research, US FDA, 3900 NCTR Rd, Jefferson, AR 72079, United States.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Beger
authors.affiliation: Division of Microbiology, National Center for Toxicological Research, US FDA, 3900 NCTR Rd, Jefferson, AR 72079, United States.
authors.forename: Carl E
authors.initials: CE
authors.lastname: Cerniglia
authors.affiliation: Office of Science, Center for Tobacco Products, US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993, United States. Electronic address: Maocheng.Yang@fda.hhs.gov.
authors.forename: Maocheng
authors.initials: M
authors.lastname: Yang
authors.affiliation: Division of Microbiology, National Center for Toxicological Research, US FDA, 3900 NCTR Rd, Jefferson, AR 72079, United States. Electronic address: Huizhong.Chen@fda.hhs.gov.
authors.forename: Huizhong
authors.initials: H
authors.lastname: Chen
mesh_terms: D002206:Capnocytophaga / Q000187:drug effects* / Q000378:metabolism; D055432:Metabolomics; D009538:Nicotine / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D014030:Tobacco, Smokeless / Q000633:toxicity*
chemical_list: D009538:Nicotine
keywords: Metabolomics; Oral bacteria; Smokeless tobacco; Toxicology