Preservation of Gastrointestinal Mucosal Barrier Function and Microbiome in Patients With Controlled HIV Infection
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...
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.688886/full |
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| author | Gerald Mak John J. Zaunders Michelle Bailey Nabila Seddiki Geraint Rogers Geraint Rogers Lex Leong Tri Giang Phan Tri Giang Phan Anthony D. Kelleher Kersten K. Koelsch Mark A. Boyd Mark A. Boyd Mark A. Boyd Mark Danta Mark Danta |
| author_facet | Gerald Mak John J. Zaunders Michelle Bailey Nabila Seddiki Geraint Rogers Geraint Rogers Lex Leong Tri Giang Phan Tri Giang Phan Anthony D. Kelleher Kersten K. Koelsch Mark A. Boyd Mark A. Boyd Mark A. Boyd Mark Danta Mark Danta |
| author_sort | Gerald Mak |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T01:15:07Z |
| format | Article |
| id | doaj.art-dadcac88cce6452bbb7cfd6c2c8c60dc |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-17T01:15:07Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-dadcac88cce6452bbb7cfd6c2c8c60dc2022-12-21T22:09:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-05-011210.3389/fimmu.2021.688886688886Preservation of Gastrointestinal Mucosal Barrier Function and Microbiome in Patients With Controlled HIV InfectionGerald Mak0John J. Zaunders1Michelle Bailey2Nabila Seddiki3Geraint Rogers4Geraint Rogers5Lex Leong6Tri Giang Phan7Tri Giang Phan8Anthony D. Kelleher9Kersten K. Koelsch10Mark A. Boyd11Mark A. Boyd12Mark A. Boyd13Mark Danta14Mark Danta15St. Vincent’s Clinical School, UNSW, Darlinghurst, NSW, AustraliaCentre for Applied Medical Research, St Vincent’s Hospital, Sydney, NSW, AustraliaKirby Institute, UNSW Sydney, Sydney, NSW, AustraliaIDMIT Department/IBFJ, Immunology of Viral Infections and Autoimmune Diseases (IMVA), INSERM U1184, CEA, Université Paris Sud, Paris, FranceSouth Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, AustraliaFaculty of Science, Flinders University, Adelaide, SA, AustraliaMicrobiology and Infectious Diseases, South Australia (SA) Pathology, Adelaide, SA, AustraliaSt. Vincent’s Clinical School, UNSW, Darlinghurst, NSW, AustraliaImmunology Division Garvan Institute of Medical Research, Sydney, NSW, AustraliaKirby Institute, UNSW Sydney, Sydney, NSW, AustraliaKirby Institute, UNSW Sydney, Sydney, NSW, AustraliaKirby Institute, UNSW Sydney, Sydney, NSW, AustraliaSouth Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, AustraliaFaculty of Health and Medical Sciences, University of Adelaide, Adelaide, SA, AustraliaSt. Vincent’s Clinical School, UNSW, Darlinghurst, NSW, Australia0Department of Gastroenterology, St. Vincent’s Hospital, Sydney, NSW, AustraliaBackgroundDespite 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.688886/fullHIVCD4antiretroviral therapy (ART)gut-associated lymphoid tissues (GALT)microbiome |
| spellingShingle | Gerald Mak John J. Zaunders Michelle Bailey Nabila Seddiki Geraint Rogers Geraint Rogers Lex Leong Tri Giang Phan Tri Giang Phan Anthony D. Kelleher Kersten K. Koelsch Mark A. Boyd Mark A. Boyd Mark A. Boyd Mark Danta Mark Danta Preservation of Gastrointestinal Mucosal Barrier Function and Microbiome in Patients With Controlled HIV Infection Frontiers in Immunology HIV CD4 antiretroviral therapy (ART) gut-associated lymphoid tissues (GALT) microbiome |
| title | Preservation of Gastrointestinal Mucosal Barrier Function and Microbiome in Patients With Controlled HIV Infection |
| title_full | Preservation of Gastrointestinal Mucosal Barrier Function and Microbiome in Patients With Controlled HIV Infection |
| title_fullStr | Preservation of Gastrointestinal Mucosal Barrier Function and Microbiome in Patients With Controlled HIV Infection |
| title_full_unstemmed | Preservation of Gastrointestinal Mucosal Barrier Function and Microbiome in Patients With Controlled HIV Infection |
| title_short | Preservation of Gastrointestinal Mucosal Barrier Function and Microbiome in Patients With Controlled HIV Infection |
| title_sort | preservation of gastrointestinal mucosal barrier function and microbiome in patients with controlled hiv infection |
| topic | HIV CD4 antiretroviral therapy (ART) gut-associated lymphoid tissues (GALT) microbiome |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.688886/full |
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