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

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 report...

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Main Authors: Gang Liu, Douglas P Lee, Eckhardt Schmidt, GL Prasad
Format: Article
Language:English
Published: SAGE Publishing 2019-10-01
Series:Bioinformatics and Biology Insights
Online Access:https://doi.org/10.1177/1177932219882961
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author Gang Liu
Douglas P Lee
Eckhardt Schmidt
GL Prasad
author_facet Gang Liu
Douglas P Lee
Eckhardt Schmidt
GL Prasad
author_sort Gang Liu
collection DOAJ
description 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.
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spelling doaj.art-13b31eb91ad74cdea48e27cb8b5c9bfc2022-12-22T02:35:10ZengSAGE PublishingBioinformatics and Biology Insights1177-93222019-10-011310.1177/1177932219882961Pathway Analysis of Global Metabolomic Profiles Identified Enrichment of Caffeine, Energy, and Arginine Metabolism in Smokers but Not Moist Snuff ConsumersGang Liu0Douglas P Lee1Eckhardt Schmidt2GL Prasad3RAI Services Company, Winston-Salem, NC, USAOmic Insight, Durham, NC, USARAI Services Company, Winston-Salem, NC, USARAI Services Company, Winston-Salem, NC, USAExisting 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.https://doi.org/10.1177/1177932219882961
spellingShingle Gang Liu
Douglas P Lee
Eckhardt Schmidt
GL Prasad
Pathway Analysis of Global Metabolomic Profiles Identified Enrichment of Caffeine, Energy, and Arginine Metabolism in Smokers but Not Moist Snuff Consumers
Bioinformatics and Biology Insights
title Pathway Analysis of Global Metabolomic Profiles Identified Enrichment of Caffeine, Energy, and Arginine Metabolism in Smokers but Not Moist Snuff Consumers
title_full Pathway Analysis of Global Metabolomic Profiles Identified Enrichment of Caffeine, Energy, and Arginine Metabolism in Smokers but Not Moist Snuff Consumers
title_fullStr Pathway Analysis of Global Metabolomic Profiles Identified Enrichment of Caffeine, Energy, and Arginine Metabolism in Smokers but Not Moist Snuff Consumers
title_full_unstemmed Pathway Analysis of Global Metabolomic Profiles Identified Enrichment of Caffeine, Energy, and Arginine Metabolism in Smokers but Not Moist Snuff Consumers
title_short Pathway Analysis of Global Metabolomic Profiles Identified Enrichment of Caffeine, Energy, and Arginine Metabolism in Smokers but Not Moist Snuff Consumers
title_sort pathway analysis of global metabolomic profiles identified enrichment of caffeine energy and arginine metabolism in smokers but not moist snuff consumers
url https://doi.org/10.1177/1177932219882961
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