Salivary metabolite levels in perinatally HIV-infected youth with periodontal disease

the Pediatric HIV/AIDS Cohort Study

doi:10.1007/s11306-020-01719-6

Salivary metabolite levels in perinatally HIV-infected youth with periodontal disease

the Pediatric HIV/AIDS Cohort Study

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

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.

Original language	English (US)
Article number	98
Journal	Metabolomics
Volume	16
Issue number	9
DOIs	https://doi.org/10.1007/s11306-020-01719-6
State	Published - Sep 1 2020

Funding

The study was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development with co-funding from the National Institute on Drug Abuse, the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, the National Institute on Deafness and Other Communication Disorders, the National Institute of Dental and Craniofacial Research, the National Cancer Institute, the National Institute on Alcohol Abuse and Alcoholism, the Office of AIDS Research, and the National Heart, Lung, and Blood Institute through cooperative agreements with the Harvard T.H. Chan School of Public Health (HD052102) (Principal Investigator: George R Seage III; Program Director: Liz Salomon) and the Tulane University School of Medicine (HD052104) (Principal Investigator: Russell Van Dyke; Co-Principal Investigator: Ellen Chadwick; Project Director: Patrick Davis). Data management services were provided by Frontier Science and Technology Research Foundation (PI: Suzanne Siminski), and regulatory services and logistical support were provided by Westat, Inc (PI: Julie Davidson). The Forsyth Center for Salivary Diagnostics was funded by the Massachusetts Life Science Center. The conclusions and opinions expressed in this article are those of the authors and do not necessarily reflect those of the National Institutes of Health or U.S. Department of Health and Human Services. Acknowledgements The Oral Health Protocol is a cross-sectional, observational sub-study within the Adolescent Master Protocol (AMP) of PHACS ( https://phacsstudy.org ) funded by the National Institutes of Health. The AMP is an ongoing prospective cohort study at 14 clinical US sites designed to determine the impact of HIV infection and antiretroviral therapy (ART) on PHIV youth. The AMP includes a comparison group of PHEU youth, for whom the mothers had HIV and were exposed to ART in utero (Siberry et al. ; Van Dyke et al. ). In this cross-sectional study, 209 PHIV and 126 PHEU participants were enrolled as reported in detail elsewhere (Moscicki et al. ). Institutional review boards (IRBs) at clinical sites and the Harvard T.H. Chan School of Public Health approved the study. Parents/legal guardians provided written informed consent for their child’s participation. Youth consented/assented per local IRB guidelines. A subset of 40 study subjects matched by age and sex was selected for this study: 10 PHIV and 10 PHEU youth with moderate periodontitis according to CDC/AAP classifications, and 10 PHIV and 10 PHEU youth without periodontal disease (Table ; Supplemental Table 1). The PHEU youth represent an important comparison group since they are exposed to HIV-infected mothers and ART in utero similarly to PHIV youth, avoiding potential confounding by these factors. We thank the children and families for their participation in PHACS, and the individuals and institutions involved in the conduct of PHACS. The following institutions, clinical site investigators and staff participated in conducting PHACS AMP and AMP Up in 2018, in alphabetical order: Ann & Robert H. Lurie Children?s Hospital of Chicago : Ellen Chadwick, Margaret Ann Sanders, Kathleen Malee, Yoonsun Pyun; Baylor College of Medicine : William Shearer, Mary Paul, Chivon McMullen-Jackson, Mandi Speer, Lynnette Harris; Bronx Lebanon Hospital Center: Murli Purswani, Mahboobullah Mirza Baig, Alma Villegas; Children's Diagnostic & Treatment Center : Lisa Gaye-Robinson, Sandra Navarro, Patricia Garvie; Boston Children?s Hospital: Sandra K. Burchett, Michelle E. Anderson, Adam R. Cassidy; Jacobi Medical Center : Andrew Wiznia, Marlene Burey, Ray Shaw, Raphaelle Auguste; Rutgers?New Jersey Medical School: Arry Dieudonne, Linda Bettica, Juliette Johnson, Karen Surowiec; St. Christopher?s Hospital for Children: Janet S. Chen, Maria Garcia Bulkley, Taesha White, Mitzie Grant; St. Jude Children's Research Hospital : Katherine Knapp, Kim Allison, Megan Wilkins, Jamie Russell-Bell; San Juan Hospital/Department of Pediatrics: Midnela Acevedo-Flores, Heida Rios, Vivian Olivera; Tulane University School of Medicine : Margarita Silio, Medea Gabriel, Patricia Sirois; University of California, San Diego : Stephen A. Spector, Megan Loughran, Veronica Figueroa, Sharon Nichols; University of Colorado Denver Health Sciences Center : Elizabeth McFarland, Carrie Chambers, Emily Barr, Mary Glidden; University of Miami: Gwendolyn Scott, Grace Alvarez, Juan Caffroni, Anai Cuadra.

Keywords

Biomarkers
HAART
HIV infection
Mass spectrometry
Periodontal disease
Targeted metabolomics

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Biochemistry
Clinical Biochemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s11306-020-01719-6

Cite this

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title = "Salivary metabolite levels in perinatally HIV-infected youth with periodontal disease",

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.",

keywords = "Biomarkers, HAART, HIV infection, Mass spectrometry, Periodontal disease, Targeted metabolomics",

author = "{the Pediatric HIV/AIDS Cohort Study} and Fabian Schulte and King, {Oliver D.} and Paster, {Bruce J.} and Moscicki, {Anna Barbara} and Yao, {Tzy Jyun} and {Van Dyke}, {Russell B.} and Caroline Shiboski and Mark Ryder and George Seage and Markus Hardt and Ellen Chadwick and Sanders, {Margaret Ann} and Kathleen Malee and Yoonsun Pyun and William Shearer and Mary Paul and Chivon McMullen-Jackson and Mandi Speer and Lynnette Harris and Murli Purswani and Baig, {Mahboobullah Mirza} and Alma Villegas and Lisa Gaye-Robinson and Sandra Navarro and Patricia Garvie and Burchett, {Sandra K.} and Anderson, {Michelle E.} and Cassidy, {Adam R.} and Andrew Wiznia and Marlene Burey and Ray Shaw and Raphaelle Auguste and Arry Dieudonne and Linda Bettica and Juliette Johnson and Karen Surowiec and Chen, {Janet S.} and Bulkley, {Maria Garcia} and Taesha White and Mitzie Grant and Katherine Knapp and Kim Allison and Megan Wilkins and Jamie Russell-Bell and Midnela Acevedo-Flores and Heida Rios and Vivian Olivera and Margarita Silio and Medea Gabriel and Patricia Sirois",

note = "Publisher Copyright: {\textcopyright} 2020, Springer Science+Business Media, LLC, part of Springer Nature.",

year = "2020",

month = sep,

day = "1",

doi = "10.1007/s11306-020-01719-6",

language = "English (US)",

volume = "16",

journal = "Metabolomics",

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TY - JOUR

T1 - Salivary metabolite levels in perinatally HIV-infected youth with periodontal disease

AU - the Pediatric HIV/AIDS Cohort Study

AU - Schulte, Fabian

AU - King, Oliver D.

AU - Paster, Bruce J.

AU - Moscicki, Anna Barbara

AU - Yao, Tzy Jyun

AU - Van Dyke, Russell B.

AU - Shiboski, Caroline

AU - Ryder, Mark

AU - Seage, George

AU - Hardt, Markus

AU - Chadwick, Ellen

AU - Sanders, Margaret Ann

AU - Malee, Kathleen

AU - Pyun, Yoonsun

AU - Shearer, William

AU - Paul, Mary

AU - McMullen-Jackson, Chivon

AU - Speer, Mandi

AU - Harris, Lynnette

AU - Purswani, Murli

AU - Baig, Mahboobullah Mirza

AU - Villegas, Alma

AU - Gaye-Robinson, Lisa

AU - Navarro, Sandra

AU - Garvie, Patricia

AU - Burchett, Sandra K.

AU - Anderson, Michelle E.

AU - Cassidy, Adam R.

AU - Wiznia, Andrew

AU - Burey, Marlene

AU - Shaw, Ray

AU - Auguste, Raphaelle

AU - Dieudonne, Arry

AU - Bettica, Linda

AU - Johnson, Juliette

AU - Surowiec, Karen

AU - Chen, Janet S.

AU - Bulkley, Maria Garcia

AU - White, Taesha

AU - Grant, Mitzie

AU - Knapp, Katherine

AU - Allison, Kim

AU - Wilkins, Megan

AU - Russell-Bell, Jamie

AU - Acevedo-Flores, Midnela

AU - Rios, Heida

AU - Olivera, Vivian

AU - Silio, Margarita

AU - Gabriel, Medea

AU - Sirois, Patricia

PY - 2020/9/1

Y1 - 2020/9/1

N2 - 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.

AB - 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.

KW - Biomarkers

KW - HAART

KW - HIV infection

KW - Mass spectrometry

KW - Periodontal disease

KW - Targeted metabolomics

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UR - http://www.scopus.com/inward/citedby.url?scp=85090905790&partnerID=8YFLogxK

U2 - 10.1007/s11306-020-01719-6

DO - 10.1007/s11306-020-01719-6

M3 - Article

C2 - 32915320

AN - SCOPUS:85090905790

SN - 1573-3882

VL - 16

JO - Metabolomics

JF - Metabolomics

IS - 9

M1 - 98

ER -

Salivary metabolite levels in perinatally HIV-infected youth with periodontal disease

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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