title: Biochemical association of metabolic profile and microbiome in chronic pressure ulcer wounds.
abstract: Chronic, non-healing wounds contribute significantly to the suffering of patients with co-morbidities in the clinical population with mild to severely compromised immune systems. Normal wound healing proceeds through a well-described process. However, in chronic wounds this process seems to become dysregulated at the transition between resolution of inflammation and re-epithelialization. Bioburden in the form of colonizing bacteria is a major contributor to the delayed headlining in chronic wounds such as pressure ulcers. However how the microbiome influences the wound metabolic landscape is unknown. Here, we have used a Systems Biology approach to determine the biochemical associations between the taxonomic and metabolomic profiles of wounds colonized by bacteria. Pressure ulcer biopsies were harvested from primary chronic wounds and bisected into top and bottom sections prior to analysis of microbiome by pyrosequencing and analysis of metabolome using 1H nuclear magnetic resonance (NMR) spectroscopy. Bacterial taxonomy revealed that wounds were colonized predominantly by three main phyla, but differed significantly at the genus level. While taxonomic profiles demonstrated significant variability between wounds, metabolic profiles shared significant similarity based on the depth of the wound biopsy. Biochemical association between taxonomy and metabolic landscape indicated significant wound-to-wound similarity in metabolite enrichment sets and metabolic pathway impacts, especially with regard to amino acid metabolism. To our knowledge, this is the first demonstration of a statistically robust correlation between bacterial colonization and metabolic landscape within the chronic wound environment.
authors.affiliation: Department of Chemistry and Biochemistry, Montana State University, Bozeman, Montana, United States of America.
authors.forename: Mary Cloud B
authors.initials: MC
authors.lastname: Ammons
authors.affiliation: Department of Chemistry and Biochemistry, Montana State University, Bozeman, Montana, United States of America.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Morrissey
authors.affiliation: Department of Chemistry and Biochemistry, Montana State University, Bozeman, Montana, United States of America.
authors.forename: Brian P
authors.initials: BP
authors.lastname: Tripet
authors.affiliation: Division of Biological Science, University of Montana, Missoula, Montana, United States of America.
authors.forename: James T
authors.initials: JT
authors.lastname: Van Leuven
authors.affiliation: Department of Dermatology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Anne
authors.initials: A
authors.lastname: Han
authors.affiliation: Department of Dermatology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Gerald S
authors.initials: GS
authors.lastname: Lazarus
authors.affiliation: Department of Dermatology, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States of America.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Zenilman
authors.affiliation: Center for Biofilm Engineering, Montana State University, Bozeman, Montana, United States of America.
authors.forename: Philip S
authors.initials: PS
authors.lastname: Stewart
authors.affiliation: Center for Biofilm Engineering, Montana State University, Bozeman, Montana, United States of America.
authors.forename: Garth A
authors.initials: GA
authors.lastname: James
authors.affiliation: Department of Chemistry and Biochemistry, Montana State University, Bozeman, Montana, United States of America.
authors.forename: Valérie
authors.initials: V
authors.lastname: Copié
mesh_terms: D039903:Actinobacteria / Q000235:genetics; D000328:Adult; D005260:Female; D000068536:Bacillota / Q000235:genetics; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D003668:Pressure Ulcer / Q000382:microbiology*; D020560:Proteobacteria / Q000235:genetics; D012336:RNA, Ribosomal, 16S; D049490:Systems Biology / Q000379:methods*; D055815:Young Adult
chemical_list: D012336:RNA, Ribosomal, 16S