title: Metabolic Consequences of Chronic Alcohol Abuse in Non-Smokers: A Pilot Study.
abstract: An alcohol use disorder (AUD) is associated with an increased susceptibility to respiratory infection and injury and, upon hospitalization, higher mortality rates. Studies in model systems show effects of alcohol on mitochondrial function, lipid metabolism and antioxidant systems. The present study applied high-resolution metabolomics to test for these changes in bronchoalveolar lavage fluid (BALF) of subjects with an AUD. Smokers were excluded to avoid confounding effects and compliance was verified by cotinine measurements. Statistically significant metabolic features, differentially expressed by control and AUD subjects, were identified by statistical and bioinformatic methods. The results show that fatty acid and acylcarnitine concentrations were increased in AUD subjects, consistent with perturbed mitochondrial and lipid metabolism. Decreased concentrations of methyl-donor compounds suggest altered one-carbon metabolism and oxidative stress. An accumulation of peptides suggests proteolytic activity, which could reflect altered epithelial barrier function. Two metabolites of possible microbial origin suggest subclinical bacterial infection. Furthermore, increased diacetylspermine suggests additional metabolic perturbations, which could contribute to dysregulated alveolar macrophage function and vulnerability to infection. Together, the results show an extended metabolic consequence of AUD in the bronchoalveolar space.
authors.affiliation: Division of Pulmonary, Allergy & Critical Care Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Obiamaka
authors.initials: O
authors.lastname: Obianyo
authors.affiliation: Division of Pulmonary, Allergy & Critical Care Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Division of Pulmonary and Critical Care, Department of Medicine, University of Colorado at Denver and Health Sciences Center, Denver, Colorado, United States of America.
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Burnham
authors.affiliation: Division of Pulmonary, Allergy & Critical Care Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America; Atlanta Veterans' Affairs and Emory University Medical Centers, Decatur, Georgia, United States of America.
authors.forename: Ashish
authors.initials: A
authors.lastname: Mehta
authors.affiliation: College of Pharmacy, Korea University, Sejong City, Korea.
authors.forename: Youngja
authors.initials: Y
authors.lastname: Park
authors.affiliation: Division of Pulmonary, Allergy & Critical Care Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Karan
authors.initials: K
authors.lastname: Uppal
authors.affiliation: Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Frank L
authors.initials: FL
authors.lastname: Harris
authors.affiliation: Division of Pulmonary, Allergy & Critical Care Medicine, Emory University School of Medicine, Atlanta, Georgia, United States of America.
authors.forename: Dean P
authors.initials: DP
authors.lastname: Jones
authors.affiliation: Division of Neonatal-Perinatal Medicine, Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, United States of America; Children's Healthcare of Atlanta Center for Developmental Lung Biology, Atlanta, Georgia, United States of America.
authors.forename: Lou Ann S
authors.initials: LA
authors.lastname: Brown
mesh_terms: D000437:Alcoholism / Q000378:metabolism*; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D002908:Chronic Disease; D006801:Humans; D050356:Lipid Metabolism; D013058:Mass Spectrometry; D055432:Metabolomics; D008928:Mitochondria / Q000502:physiology; D018384:Oxidative Stress; D010865:Pilot Projects; D012907:Smoking
chemical_list: D000975:Antioxidants; D015415:Biomarkers