Oral and Gut Microbial Diversity and Immune Regulation in Patients with HIV on Antiretroviral Therapy
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Annavajhala MK, Khan SD, Sullivan SB, Shah J, Pass L, Kister K, Kunen H, Chiang V, Monnot GC, Ricupero CL, Mazur RA, Gordon P, de Jong A, Wadhwa S, Yin MT, Demmer RT, Uhlemann AC
Journal
mSphere
Year
2020
Keywords:
HIV, antiretroviral agents, antiretroviral therapy, immune dysfunction, immune system activation, mycobiome, oral microbiome
Despite evidence of a chronic inflammatory phenotype in people living with HIV (PLWH) on antiretroviral therapy (ART), the role of oral microbiota in chronic immune activation has not been fully explored. We aimed to determine the relationship between oral and gut microbiome diversity and chronic systemic inflammation in ART-treated PLWH with prevalent severe periodontitis, an inflammatory condition commonly associated with HIV infection. We assessed bacterial and fungal communities at oral and gastrointestinal sites in a cohort (n = 52) of primarily postmenopausal women on ART using 16S rRNA and internal transcribed spacer (ITS) sequencing and measured cellular and soluble markers of inflammation and immune dysfunction. Linear mixed-effect regression and differential abundance analyses were used to associate clinical characteristics and immunological markers with bacterial and fungal diversity and community composition. Bacterial α-diversity in plaque, saliva, and gut was associated with different immunological markers, while mycobial diversity was not associated with soluble or cellular biomarkers of immune stimulation or T cell dysfunction. Furthermore, lipopolysaccharide-positive (LPS+) bacteria previously linked to inflammatory outcomes were enriched at oral sites in patients with severe periodontitis. Fungal α-diversity was reduced in plaque from teeth with higher clinical attachment loss, a marker of periodontitis, and in saliva and plaque from patients with a history of AIDS. Our results show that both bacterial and fungal oral microbiome communities likely play a role in chronic systemic immune activation in PLWH. Thus, interventions targeting both inflammation and the microbiome, particularly in the oral cavity, may be necessary to reduce chronic immune dysregulation in patients with HIV.IMPORTANCE 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.
Statistical test
PERMANOVA
Experiment 1
Needs review
Subjects
- Location of subjects
- United States of America
- Host species Species from which microbiome was sampled (if applicable)
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Oral cavity Bucca,Buccal cavity,Cavity of mouth,Oral cavity
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- HIV infection [X]Human immunodeficiency virus disease,[X]Human immunodeficiency virus disease (disorder),[X]Unspecified human immunodeficiency virus [HIV] disease,[X]Unspecified human immunodeficiency virus [HIV] disease (disorder),HIV - Human immunodeficiency virus infection,HIV INFECT,HIV Infection,HIV infection,HIV Infections,HIV infectious disease,HTLV III INFECT,HTLV III Infections,HTLV III LAV INFECT,HTLV III LAV Infections,HTLV WIII INFECTIONS,HTLV WIII LAV INFECTIONS,HTLV-III Infection,HTLV-III Infections,HTLV-III-LAV Infection,HTLV-III-LAV Infections,HUMAN IMMUNO VIRUS DIS,human immunodeficiency virus,Human immunodeficiency virus [HIV] disease,HUMAN IMMUNOdeficiency VIRUS [HIV] INFECTION,Human immunodeficiency virus caused disease or disorder,Human immunodeficiency virus disease,Human immunodeficiency virus disease (disorder),Human immunodeficiency virus disease or disorder,Human immunodeficiency virus infection,Human immunodeficiency virus infection (disorder),Human immunodeficiency virus infection, NOS,Human immunodeficiency virus infectious disease,human immunodeficiency virus infectious disease,Infection, HIV,Infection, HTLV-III,Infection, HTLV-III-LAV,Infections, HIV,Infections, HTLV-III,Infections, HTLV-III-LAV,LYMPHOTROPIC VIRUS TYPE III INFECTIONS HUMAN T,T LYMPHOTROPIC VIRUS TYPE III INFECT HUMAN,T Lymphotropic Virus Type III Infections, Human,T-Lymphotropic Virus Type III Infections, Human,Unspecified human immunodeficiency virus [HIV] disease (disorder)
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- PLWH >50 years old with no/mild periodontitis
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- PLWH >50 years old with severe periodontitis
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Periodontal disease severity categories as defined by the Centers for Disease Control and Prevention (CDC) and the American Academy of Periodontology (AAP)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 4
- Group 1 sample size Number of subjects in the case (exposed) group
- 22
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V3-V4
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- .05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
- Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
- age, race, sex
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- decreased
Signature 1
Needs review
Source: Table S6 Supplemental Text
Description: Relative Abundance between severe and no/mild periodontal disease
Abundance in Group 1: increased abundance in PLWH >50 years old with severe periodontitis
| NCBI | Quality Control | Links |
|---|---|---|
| Candida albicans | ||
| Candida parapsilosis | ||
| Filobasidiales |
Revision editor(s): Jacquelynshevin
Signature 2
Needs review
Source: Table S6 Supplemental Text
Description: Relative Abundance between severe and no/mild periodontal disease
Abundance in Group 1: decreased abundance in PLWH >50 years old with severe periodontitis
| NCBI | Quality Control | Links |
|---|---|---|
| Candida dubliniensis | ||
| Exserohilum turcicum | ||
| Tausonia pullulans | ||
| Debaryomyces hansenii |
Revision editor(s): Jacquelynshevin
Signature 3
Needs review
Source: Table S5 Supplemental Text
Description: Relative Abundance between severe and no/mild periodontal disease
Abundance in Group 1: increased abundance in PLWH >50 years old with severe periodontitis
| NCBI | Quality Control | Links |
|---|---|---|
| Fusobacterium | ||
| Kingella | ||
| Prevotella | ||
| Prevotella melaninogenica | ||
| Rothia dentocariosa | ||
| Rothia mucilaginosa | ||
| Streptococcus | ||
| Veillonella | ||
| Veillonella dispar |
Revision editor(s): Jacquelynshevin
Signature 4
Needs review
Source: Table S5 Supplemental Text
Description: Relative Abundance between severe and no/mild periodontal disease
Abundance in Group 1: decreased abundance in PLWH >50 years old with severe periodontitis
| NCBI | Quality Control | Links |
|---|---|---|
| Megasphaera | ||
| Veillonella dispar |
Revision editor(s): Jacquelynshevin
Signature 5
Needs review
Source: Table S8 Supplemental Text
Description: Relative Abundance between severe and no/mild periodontal disease
Abundance in Group 1: increased abundance in PLWH >50 years old with severe periodontitis
| NCBI | Quality Control | Links |
|---|---|---|
| Streptococcus |
Revision editor(s): Jacquelynshevin
Signature 6
Needs review
Source: Table S8 Supplemental Text
Description: Relative Abundance between severe and no/mild periodontal disease
Abundance in Group 1: decreased abundance in PLWH >50 years old with severe periodontitis
| NCBI | Quality Control | Links |
|---|---|---|
| Rothia mucilaginosa | ||
| Neisseria |
Revision editor(s): Jacquelynshevin
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