Oral and Gut Microbial Diversity and Immune Regulation in Patients with HIV on Antiretroviral Therapy

Author:

Annavajhala Medini K.12,Khan Sabrina D.12,Sullivan Sean B.12,Shah Jayesh1,Pass Lauren3,Kister Karolina3,Kunen Heather3,Chiang Victor3,Monnot Gwennaëlle C.4,Ricupero Christopher L.3,Mazur Rebecca A.3,Gordon Peter1,de Jong Annemieke4,Wadhwa Sunil3,Yin Michael T.1,Demmer Ryan T.5,Uhlemann Anne-Catrin12ORCID

Affiliation:

1. Department of Medicine, Division of Infectious Diseases, Columbia University Medical Center, New York, New York, USA

2. Microbiome and Pathogen Genomics Core, Columbia University Medical Center, New York, New York, USA

3. Department of Orthodontics, School of Dental Medicine, Columbia University Medical Center, New York, New York, USA

4. Department of Dermatology, Columbia University Medical Center, New York, New York, USA

5. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA

Abstract

A feedback loop between dysbiotic gut microbiota, increased translocation of microbial products such as lipopolysaccharide, and inflammation has been hypothesized to cause immune system dysfunction in early HIV infection. However, despite evidence of a chronic inflammatory phenotype in patients on antiretroviral therapy (ART), the role of oral microbiota in systemic immune activation and the relationship between oral and gut bacterial and fungal diversity have not been explored. Our study suggests a crucial role for oral bacterial and fungal communities in long-term systemic immune activation in patients on ART, expanding the current paradigm focused on gut bacteria. Our results indicate that interventions targeting both inflammation and microbial diversity are needed to mitigate oral inflammation-related comorbidities, particularly in HIV-positive patients. More broadly, these findings can bolster general models of microbiome-mediated chronic systemic immune activation and aid the development of precise microbiota-targeted interventions to reverse chronic inflammation.

Funder

HHS | NIH | National Center for Advancing Translational Sciences

HHS | NIH | National Institute of Dental and Craniofacial Research

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology

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