Fabian Schulte1,2, Oliver D King3, Bruce J Paster1, Anna-Barbara Moscicki4, Tzy-Jyun Yao5, Russell B Van Dyke6, Caroline Shiboski7, Mark Ryder7, George Seage8, Markus Hardt9,10. 1. Forsyth Center for Salivary Diagnostics, Department of Applied Oral Sciences, The Forsyth Institute, 245 First Street, Cambridge, MA, USA. 2. Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA, USA. 3. Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA. 4. Department of Pediatrics, Division of Adolescent and Young Adult Medicine, University of California, Los Angeles, CA, USA. 5. Center for Biostatistics in AIDS Research, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 6. School of Medicine, Tulane University, New Orleans, LA, USA. 7. Department of Orofacial Sciences, School of Dentistry, University of California, San Francisco, CA, USA. 8. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 9. Forsyth Center for Salivary Diagnostics, Department of Applied Oral Sciences, The Forsyth Institute, 245 First Street, Cambridge, MA, USA. mhardt@forsyth.org. 10. Department of Developmental Biology, Harvard School of Dental Medicine, Boston, MA, USA. mhardt@forsyth.org.
Abstract
INTRODUCTION: Salivary metabolite profiles are altered in adults with HIV compared to their uninfected counterparts. Less is known about youth with HIV and how oral disorders that commonly accompany HIV infection impact salivary metabolite levels. OBJECTIVE: As part of the Adolescent Master Protocol multi-site cohort study of the Pediatric HIV/AIDS Cohort Study (PHACS) network we compared the salivary metabolome of youth with perinatally-acquired HIV (PHIV) and youth HIV-exposed, but uninfected (PHEU) and determined whether metabolites differ in PHIV versus PHEU. METHODS: We used three complementary targeted and discovery-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) workflows to characterize salivary metabolite levels in 20 PHIV and 20 PHEU youth with and without moderate periodontitis. We examined main effects associated with PHIV and periodontal disease, and the interaction between them. RESULTS: We did not identify differences in salivary metabolite profiles that remained significant under stringent control for both multiple between-group comparisons and multiple metabolites. Levels of cadaverine, a known periodontitis-associated metabolite, were more abundant in individuals with periodontal disease with the difference being more pronounced in PHEU than PHIV. In the discovery-based dataset, we identified a total of 564 endogenous peptides in the metabolite extracts, showing that proteolytic processing and amino acid metabolism are important to consider in the context of HIV infection. CONCLUSION: The salivary metabolite profiles of PHIV and PHEU youth were overall very similar. Individuals with periodontitis particularly among the PHEU youth had higher levels of cadaverine, suggesting that HIV infection, or its treatment, may influence the metabolism of oral bacteria.
INTRODUCTION: Salivary metabolite profiles are altered in adults with HIV compared to their uninfected counterparts. Less is known about youth with HIV and how oral disorders that commonly accompany HIV infection impact salivary metabolite levels. OBJECTIVE: As part of the Adolescent Master Protocol multi-site cohort study of the Pediatric HIV/AIDS Cohort Study (PHACS) network we compared the salivary metabolome of youth with perinatally-acquired HIV (PHIV) and youth HIV-exposed, but uninfected (PHEU) and determined whether metabolites differ in PHIV versus PHEU. METHODS: We used three complementary targeted and discovery-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) workflows to characterize salivary metabolite levels in 20 PHIV and 20 PHEU youth with and without moderate periodontitis. We examined main effects associated with PHIV and periodontal disease, and the interaction between them. RESULTS: We did not identify differences in salivary metabolite profiles that remained significant under stringent control for both multiple between-group comparisons and multiple metabolites. Levels of cadaverine, a known periodontitis-associated metabolite, were more abundant in individuals with periodontal disease with the difference being more pronounced in PHEU than PHIV. In the discovery-based dataset, we identified a total of 564 endogenous peptides in the metabolite extracts, showing that proteolytic processing and amino acid metabolism are important to consider in the context of HIV infection. CONCLUSION: The salivary metabolite profiles of PHIV and PHEU youth were overall very similar. Individuals with periodontitis particularly among the PHEU youth had higher levels of cadaverine, suggesting that HIV infection, or its treatment, may influence the metabolism of oral bacteria.
Entities:
Keywords:
Biomarkers; HAART; HIV infection; Mass spectrometry; Periodontal disease; Targeted metabolomics
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