Preservation of Gastrointestinal Mucosal Barrier Function and Microbiome in Patients With Controlled HIV Infection

Autor: Gerald Mak, John J. Zaunders, Michelle Bailey, Nabila Seddiki, Geraint Rogers, Lex Leong, Tri Giang Phan, Anthony D. Kelleher, Kersten K. Koelsch, Mark A. Boyd, Mark Danta
Rok vydání: 2021
Předmět:
CD4-Positive T-Lymphocytes
Male
0301 basic medicine
Lipopolysaccharide Receptors
microbiome
HIV Infections
Pilot Projects
CD8-Positive T-Lymphocytes
CD38
Gut flora
antiretroviral therapy (ART)
Systemic inflammation
0302 clinical medicine
Immunophenotyping
Immunology and Allergy
Medicine
Intestinal Mucosa
Barrier function
Original Research
biology
Middle Aged
Treatment Outcome
030211 gastroenterology & hepatology
medicine.symptom
Adult
Anti-HIV Agents
Lymphoid Tissue
Immunology
Inflammation
Permeability
HIV Long-Term Survivors
03 medical and health sciences
Humans
Microbiome
Immunity
Mucosal
gut-associated lymphoid tissues (GALT)
Interleukin-6
Tumor Necrosis Factor-alpha
business.industry
HIV
RC581-607
biology.organism_classification
CD4
Gastrointestinal Microbiome
Cross-Sectional Studies
030104 developmental biology
Bacterial Translocation
Case-Control Studies
Immunologic diseases. Allergy
business
Biomarkers
CD8
Zdroj: Frontiers in Immunology, Vol 12 (2021)
Frontiers in Immunology
ISSN: 1664-3224
DOI: 10.3389/fimmu.2021.688886
Popis: BackgroundDespite successful ART in people living with HIV infection (PLHIV) they experience increased morbidity and mortality compared with HIV-negative controls. A dominant paradigm is that gut-associated lymphatic tissue (GALT) destruction at the time of primary HIV infection leads to loss of gut integrity, pathological microbial translocation across the compromised gastrointestinal barrier and, consequently, systemic inflammation. We aimed to identify and measure specific changes in the gastrointestinal barrier that might allow bacterial translocation, and their persistence despite initiation of antiretroviral therapy (ART).MethodWe conducted a cross-sectional study of the gastrointestinal (GIT) barrier in PLHIV and HIV-uninfected controls (HUC). The GIT barrier was assessed as follows: in vivo mucosal imaging using confocal endomicroscopy (CEM); the immunophenotype of GIT and circulating lymphocytes; the gut microbiome; and plasma inflammation markers Tumour Necrosis Factor-α (TNF-α) and Interleukin-6 (IL-6); and the microbial translocation marker sCD14.ResultsA cohort of PLHIV who initiated ART early, during primary HIV infection (PHI), n=5), and late (chronic HIV infection (CHI), n=7) infection were evaluated for the differential effects of the stage of ART initiation on the GIT barrier compared with HUC (n=6). We observed a significant decrease in the CD4 T-cell count of CHI patients in the left colon (p=0.03) and a trend to a decrease in the terminal ileum (p=0.13). We did not find evidence of increased epithelial permeability by CEM. No significant differences were found in microbial translocation or inflammatory markers in plasma. In gut biopsies, CD8 T-cells, including resident intraepithelial CD103+ cells, did not show any significant elevation of activation in PLHIV, compared to HUC. The majority of residual circulating activated CD38+HLA-DR+ CD8 T-cells did not exhibit gut-homing integrins α4ß7, suggesting that they did not originate in GALT. A significant reduction in the evenness of species distribution in the microbiome of CHI subjects (p=0.016) was observed, with significantly higher relative abundance of the genus Spirochaeta in PHI subjects (p=0.042).ConclusionThese data suggest that substantial, non-specific increases in epithelial permeability may not be the most important mechanism of HIV-associated immune activation in well-controlled HIV-positive patients on antiretroviral therapy. Changes in gut microbiota warrant further study.
Databáze: OpenAIRE
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