title: Metabolomics reveals differential levels of oral metabolites in HIV-infected patients: toward novel diagnostic targets.
abstract: The objective of the current study was to characterize the profile of oral metabolites in HIV-infected patients using metabolomics. Oral wash samples were collected from 12 HIV-infected and 12 healthy individuals (matched for age, sex, and ethnicity), processed, and analyzed by metabolomics. We detected 198 identifiable and 85 nonidentifiable metabolites; 27 identifiable metabolites were differentially present (12 increased, 15 decreased) in HIV-infected patients. Elevated metabolites included p-cresol sulfate, nucleotides (e.g., allantoin), and amino acids (e.g., phenylalanine, tryptophan), whereas decreased oral metabolites included fucose, fumarate, and N-acetylglucosamine. Pathway network analysis revealed the largest multinode network in healthy versus HIV-infected patients to involve carbohydrate biosynthesis and degradation. HIV-infected patients on antiretroviral therapy (ART) showed the largest number (12) of statistically significant metabolite correlation differences compared with healthy controls. Interestingly, the oral phenlyalanine:tyrosine ratio increased in ART-naive HIV-infected patients (mean ± SEM = 2.58 ± 0.87) compared with healthy individuals (1.33 ± 0.10, p = 0.062) or ART-experienced patients (1.78 ± 0.30, p = 0.441). This is the first study to reveal differential levels of oral metabolites in HIV-infected patients compared withj healthy volunteers, and that oral phenlyalanine:tyrosine ratio may be a useful marker for noninvasive monitoring of the immune status during HIV infection.
authors.affiliation: Center for Medical Mycology, Case Western Reserve University, Ohio 44106-5028, USA. Mahmoud.Ghannoum@case.edu
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Ghannoum
authors.forename: Pranab K
authors.initials: PK
authors.lastname: Mukherjee
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Jurevic
authors.forename: Mauricio
authors.initials: M
authors.lastname: Retuerto
authors.forename: Robert E
authors.initials: RE
authors.lastname: Brown
authors.forename: Masoumeh
authors.initials: M
authors.lastname: Sikaroodi
authors.forename: Jennifer
authors.initials: J
authors.lastname: Webster-Cyriaque
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Gillevet
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics; D008875:Middle Aged; D009055:Mouth / Q000378:metabolism*; D010649:Phenylalanine / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D014443:Tyrosine; D010649:Phenylalanine