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Pathway Analysis of Global Metabolomic Profiles Identified Enrichment of Caffeine, Energy, and Arginine Metabolism in Smokers but Not Moist Snuff Consumers.

ABSTRACT: Existing US epidemiological data demonstrate that consumption of smokeless tobacco, particularly moist snuff, is less harmful than cigarette smoking. However, the molecular and biochemical changes due to moist snuff consumption relative to smoking remain incompletely understood. We previously reported that smokers (SMK) exhibit elevated oxidative stress and inflammation relative to moist snuff consumers (MSC) and non-tobacco consumers (NTC), based on metabolomic profiling data of saliva, plasma, and urine from MSC, SMK, and NTC. In this study, we investigated the effects of tobacco consumption on additional metabolic pathways using pathway-based analysis tools. To this end, metabolic pathway enrichment analysis and topology analysis were performed through pair-wise comparisons of global metabolomic profiles of SMK, MSC, and NTC. The analyses identified >8 significantly perturbed metabolic pathways in SMK compared with NTC and MSC in all 3 matrices. Among these differentially enriched pathways, perturbations of caffeine metabolism, energy metabolism, and arginine metabolism were mostly observed. In comparison, fewer enriched metabolic pathways were identified in MSC compared with NTC (5 in plasma, none in urine and saliva). This is consistent with our transcriptomics profiling results that show no significant differences in peripheral blood mononuclear cell gene expression between MSC and NTC. These findings, taken together with our previous biochemical, metabolomic, and transcriptomic analysis results, provide a better understanding of the relative changes in healthy tobacco consumers, and demonstrate that chronic cigarette smoking, relative to the use of smokeless tobacco, results in more pronounced biological changes, which could culminate in smoking-related diseases.

SUBMITTER: Liu G

PROVIDER: S-EPMC6798164 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Pathway Analysis of Global Metabolomic Profiles Identified Enrichment of Caffeine, Energy, and Arginine Metabolism in Smokers but Not Moist Snuff Consumers.

Liu Gang G Lee Douglas P DP Schmidt Eckhardt E Prasad G L GL

Bioinformatics and biology insights 20191017

Existing US epidemiological data demonstrate that consumption of smokeless tobacco, particularly moist snuff, is less harmful than cigarette smoking. However, the molecular and biochemical changes due to moist snuff consumption relative to smoking remain incompletely understood. We previously reported that smokers (SMK) exhibit elevated oxidative stress and inflammation relative to moist snuff consumers (MSC) and non-tobacco consumers (NTC), based on metabolomic profiling data of saliva, plasma, ...[more]

PMID: 31666793

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Project description:BackgroundSmokeless tobacco (ST) products are widely used throughout the world and contribute to morbidity and mortality in users through an increased risk of cancers and oral diseases. Bacterial populations in ST contribute to taste, but their presence can also create carcinogenic, Tobacco-Specific N-nitrosamines (TSNAs). Previous studies of microbial communities in tobacco products lacked chemistry data (e.g. nicotine, TSNAs) to characterize the products and identify associations between carcinogen levels and taxonomic groups. This study uses statistical analysis to identify potential associations between microbial and chemical constituents in moist snuff products.MethodsWe quantitatively analyzed 38 smokeless tobacco products for TSNAs using liquid chromatography with tandem mass spectrometry (LC-MS/MS), and nicotine using gas chromatography with mass spectrometry (GC-MS). Moisture content determinations (by weight loss on drying), and pH measurements were also performed. We used 16S rRNA gene sequencing to characterize the microbial composition, and additionally measured total 16S bacterial counts using a quantitative PCR assay.ResultsOur findings link chemical constituents to their associated bacterial populations. We found core taxonomic groups often varied between manufacturers. When manufacturer and flavor were controlled for as confounding variables, the genus Lactobacillus was found to be positively associated with TSNAs. while the genera Enteractinococcus and Brevibacterium were negatively associated. Three genera (Corynebacterium, Brachybacterium, and Xanthomonas) were found to be negatively associated with nicotine concentrations. Associations were also investigated separately for products from each manufacturer. Products from one manufacturer had a positive association between TSNAs and bacteria in the genus Marinilactibacillus. Additionally, we found that TSNA levels in many products were lower compared with previously published chemical surveys. Finally, we observed consistent results when either relative or absolute abundance data were analyzed, while results from analyses of log-ratio-transformed abundances were divergent.

Project description:Use of smokeless tobacco products (STPs) is associated with oral cavity cancer and other health risks. Comprehensive analysis for chemical composition and toxicity is needed to compare conventional and newer STPs with lower tobacco-specific nitrosamines (TSNAs) yields. Seven conventional and 12 low-TSNA moist snuff products purchased in the U.S., Sweden, and South Africa were analyzed for 18 chemical constituents (International Agency for Research on Cancer classified carcinogens), pH, nicotine, and free nicotine. Chemicals were compared in each product using Wilcoxon rank-sum test and principle component analysis (PCA). Conventional compared to low-TSNA moist snuff products had higher ammonia, benzo[a]pyrene, cadmium, nickel, nicotine, nitrate, and TSNAs and had lower arsenic in dry weight content and per mg nicotine. Lead and chromium were significantly higher in low-TSNA moist snuff products. PCA showed a clear difference for constituents between conventional and low-TSNA moist snuff products. Differences among products were reduced when considered on a per mg nicotine basis. As one way to contextualize differences in constituent levels, probabilistic lifetime cancer risk was estimated for chemicals included in The University of California's carcinogenic potency database (CPDB). Estimated probabilistic cancer risks were 3.77-fold or 3-fold higher in conventional compared to low-TSNA moist snuff products under dry weight or under per mg nicotine content, respectively. In vitro testing for the STPs indicated low level toxicity and no substantial differences. The comprehensive chemical characterization of both conventional and low-TSNA moist snuff products from this study provides a broader assessment of understanding differences in carcinogenic potential of the products. In addition, the high levels and probabilistic cancer risk estimates for certain chemical constituents of smokeless tobacco products will further inform regulatory decision makers and aid them in their efforts to reduce carcinogen exposure in smokeless tobacco products.

Project description:IntroductionTobacco product characteristics convey product attributes to potential users. This study aimed to assess independent contributions of specific e-cigarette and smokeless tobacco product characteristics to adolescents' perceptions about these products.MethodsIn 2019-2020, students (N=1003) attending a convenience sample of 7 high schools in California (USA) were individually randomized to one of two discrete choice experiments, featuring either electronic cigarettes (e-cigarettes) or moist snuff. Participants were presented like-product pairs of randomlygenerated hypothetical tobacco products differing in device type, flavor, vapor cloud, and nicotine amount (for e-cigarettes) or differing in brand, flavor, cut, and price (for moist snuff). Within pairs, participants were asked about which product they were more curious, was more dangerous, would give a greater 'buzz,' and would be easier to use. Conditional logistic regression was used to quantify independent associations of product characteristics to participants' choices.ResultsEach e-cigarette and moist snuff characteristic was independently associated with multiple product perceptions. All non-tobacco flavors were associated with more curiosity and perceived ease-of-use but lower perceived danger. Tank and pod-type e-cigarettes were viewed as easier to use and garnered more curiosity than 'cigalike' or 'drip-mod' devices. Smaller vapor cloud e-cigarettes and lower-price moist snuff were viewed as less dangerous, less buzz-inducing, and easier to use. Product ever users held stronger perceptions than never users about device type (e-cigarettes) and brands (moist snuff), while product naïve participants more strongly associated flavor with danger and buzz.ConclusionsTobacco product characteristics convey product attributes to adolescents that may increase appeal. Restricting specific characteristics, including flavors, could reduce positive perceptions of these products among youth.

Project description:IntroductionCurrently, there is no widely accepted, non-self-report measure that simultaneously reflects smoking behaviors and is molecularly informative of general disease processes. Recently, researchers developed a smoking index (SI) using nucleated blood cells and a multi-tissue DNA methylation-based predictor of chronological age and disease (DNA methylation age [DNAm-age]). To better understand the utility of this novel SI in readily accessible cell types, we used buccal cell DNA methylation to examine SI relationships with long-term tobacco smoking and moist snuff consumption.MethodsWe used a publicly available dataset composed of buccal cell DNA methylation values from 120 middle-aged men (40 long-term smokers, 40 moist snuff consumers, and 40 nonsmokers). DNAm-age (353-CpGs) and SI (66-CpGs) were calculated using CpG sites measured using the Illumina HumanMethylation450 BeadChip. We estimated associations of tobacco consumption habits with both SI and DNAm-age using linear regression models adjusted for chronological age, race, and methylation technical covariates.ResultsIn fully adjusted models with nonsmokers as the reference, smoking (β = 1.08, 95% CI = 0.82 to 1.33, p < .0001) but not snuff consumption (β = .06, 95% CI = -0.19 to 0.32, p = .63) was significantly associated with SI. SI was an excellent predictor of smoking versus nonsmoking (area under the curve = 0.92, 95% CI = 0.85 to 0.98). Four DNAm-age CpGs were differentially methylated between smokers and nonsmokers including cg14992253 [EIF3I], which has been previously shown to be differentially methylated with exposure to long-term fine-particle air pollution (PM2.5).ConclusionsThe 66-CpG SI appears to be a useful tool for measuring smoking-specific behaviors in buccal cells. Still, further research is needed to broadly confirm our findings and SI relationships with DNAm-age.ImplicationsOur findings demonstrate that this 66-CpG blood-derived SI can reflect long-term tobacco smoking, but not long-term snuff consumption, in buccal cells. This evidence will be useful as the field works to identify an accurate non-self-report smoking biomarker that can be measured in an easily accessible tissue. Future research efforts should focus on (1) optimizing the relationship of the SI with DNAm-age so that the metric can maximize its utility as a tool for understanding general disease processes, and (2) determining normal values for the SI CpGs so that the measure is not as study sample specific.

Dataset Information

Pathway Analysis of Global Metabolomic Profiles Identified Enrichment of Caffeine, Energy, and Arginine Metabolism in Smokers but Not Moist Snuff Consumers.

Publications

Pathway Analysis of Global Metabolomic Profiles Identified Enrichment of Caffeine, Energy, and Arginine Metabolism in Smokers but Not Moist Snuff Consumers.

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