Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/131093
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Type: Journal article
Title: Preservation of gastrointestinal mucosal barrier function and microbiome in patients with controlled HIV infection
Author: Mak, G.
Zaunders, J.J.
Bailey, M.
Seddiki, N.
Rogers, G.
Leong, L.
Phan, T.G.
Kelleher, A.D.
Koelsch, K.K.
Boyd, M.A.
Danta, M.
Citation: Frontiers in Immunology, 2021; 12:688886-1-688886-15
Publisher: Frontiers Media
Issue Date: 2021
ISSN: 1664-3224
1664-3224
Statement of
Responsibility: 
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, and Mark Danta
Abstract: Background: Despite 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). Method: We 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. Results: A 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). Conclusion: These 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.
Keywords: HIV; CD4; antiretroviral therapy (ART); gut-associated lymphoid tissues (GALT); microbiome
Rights: © 2021 Mak, Zaunders, Bailey, Seddiki, Rogers, Leong, Phan, Kelleher, Koelsch, Boyd and Danta. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
RMID: 1000042615
DOI: 10.3389/fimmu.2021.688886
Grant ID: http://purl.org/au-research/grants/arc/LP10020080
http://purl.org/au-research/grants/nhmrc/1155678
http://purl.org/au-research/grants/nhmrc/1063422
http://purl.org/au-research/grants/nhmrc/1052979
Appears in Collections:Medicine publications

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