Cargando…

Markers of Gut Barrier Function and Microbial Translocation Associate with Lower Gut Microbial Diversity in People with HIV

People with human immunodeficiency virus (HIV) (PWH) have reduced gut barrier integrity (“leaky gut”) that permits diffusion of microbial antigens (microbial translocation) such as lipopolysaccharide (LPS) into the circulation, stimulating inflammation. A potential source of this disturbance, in add...

Descripción completa

Detalles Bibliográficos
Autores principales: Ellis, Ronald J., Iudicello, Jennifer E., Heaton, Robert K., Isnard, Stéphane, Lin, John, Routy, Jean-Pierre, Gianella, Sara, Hoenigl, Martin, Knight, Rob
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8537977/
https://www.ncbi.nlm.nih.gov/pubmed/34696320
http://dx.doi.org/10.3390/v13101891
_version_ 1784588397335019520
author Ellis, Ronald J.
Iudicello, Jennifer E.
Heaton, Robert K.
Isnard, Stéphane
Lin, John
Routy, Jean-Pierre
Gianella, Sara
Hoenigl, Martin
Knight, Rob
author_facet Ellis, Ronald J.
Iudicello, Jennifer E.
Heaton, Robert K.
Isnard, Stéphane
Lin, John
Routy, Jean-Pierre
Gianella, Sara
Hoenigl, Martin
Knight, Rob
author_sort Ellis, Ronald J.
collection PubMed
description People with human immunodeficiency virus (HIV) (PWH) have reduced gut barrier integrity (“leaky gut”) that permits diffusion of microbial antigens (microbial translocation) such as lipopolysaccharide (LPS) into the circulation, stimulating inflammation. A potential source of this disturbance, in addition to gut lymphoid tissue CD4+ T-cell depletion, is the interaction between the gut barrier and gut microbes themselves. We evaluated the relationship of gut barrier integrity, as indexed by plasma occludin levels (higher levels corresponding to greater loss of occludin from the gut barrier), to gut microbial diversity. PWH and people without HIV (PWoH) participants were recruited from community sources and provided stool, and 16S rRNA amplicon sequencing was used to characterize the gut microbiome. Microbial diversity was indexed by Faith’s phylogenetic diversity (PD). Participants were 50 PWH and 52 PWoH individuals, mean ± SD age 45.6 ± 14.5 years, 28 (27.5%) women, 50 (49.0%) non-white race/ethnicity. PWH had higher gut microbial diversity (Faith’s PD 14.2 ± 4.06 versus 11.7 ± 3.27; p = 0.0007), but occludin levels were not different (1.84 ± 0.311 versus 1.85 ± 0.274; p = 0.843). Lower gut microbial diversity was associated with higher plasma occludin levels in PWH (r = −0.251; p = 0.0111), but not in PWoH. A multivariable model demonstrated an interaction (p = 0.0459) such that the correlation between Faith’s PD and plasma occludin held only for PWH (r = −0.434; p = 0.0017), but not for PWoH individuals (r = −0.0227; p = 0.873). The pattern was similar for Shannon alpha diversity. Antiretroviral treatment and viral suppression status were not associated with gut microbial diversity (ps > 0.10). Plasma occludin levels were not significantly related to age, sex or ethnicity, nor to current or nadir CD4 or plasma viral load. Higher occludin levels were associated with higher plasma sCD14 and LPS, both markers of microbial translocation. Together, the findings suggest that damage to the gut epithelial barrier is an important mediator of microbial translocation and inflammation in PWH, and that reduced gut microbiome diversity may have an important role.
format Online
Article
Text
id pubmed-8537977
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-85379772021-10-24 Markers of Gut Barrier Function and Microbial Translocation Associate with Lower Gut Microbial Diversity in People with HIV Ellis, Ronald J. Iudicello, Jennifer E. Heaton, Robert K. Isnard, Stéphane Lin, John Routy, Jean-Pierre Gianella, Sara Hoenigl, Martin Knight, Rob Viruses Article People with human immunodeficiency virus (HIV) (PWH) have reduced gut barrier integrity (“leaky gut”) that permits diffusion of microbial antigens (microbial translocation) such as lipopolysaccharide (LPS) into the circulation, stimulating inflammation. A potential source of this disturbance, in addition to gut lymphoid tissue CD4+ T-cell depletion, is the interaction between the gut barrier and gut microbes themselves. We evaluated the relationship of gut barrier integrity, as indexed by plasma occludin levels (higher levels corresponding to greater loss of occludin from the gut barrier), to gut microbial diversity. PWH and people without HIV (PWoH) participants were recruited from community sources and provided stool, and 16S rRNA amplicon sequencing was used to characterize the gut microbiome. Microbial diversity was indexed by Faith’s phylogenetic diversity (PD). Participants were 50 PWH and 52 PWoH individuals, mean ± SD age 45.6 ± 14.5 years, 28 (27.5%) women, 50 (49.0%) non-white race/ethnicity. PWH had higher gut microbial diversity (Faith’s PD 14.2 ± 4.06 versus 11.7 ± 3.27; p = 0.0007), but occludin levels were not different (1.84 ± 0.311 versus 1.85 ± 0.274; p = 0.843). Lower gut microbial diversity was associated with higher plasma occludin levels in PWH (r = −0.251; p = 0.0111), but not in PWoH. A multivariable model demonstrated an interaction (p = 0.0459) such that the correlation between Faith’s PD and plasma occludin held only for PWH (r = −0.434; p = 0.0017), but not for PWoH individuals (r = −0.0227; p = 0.873). The pattern was similar for Shannon alpha diversity. Antiretroviral treatment and viral suppression status were not associated with gut microbial diversity (ps > 0.10). Plasma occludin levels were not significantly related to age, sex or ethnicity, nor to current or nadir CD4 or plasma viral load. Higher occludin levels were associated with higher plasma sCD14 and LPS, both markers of microbial translocation. Together, the findings suggest that damage to the gut epithelial barrier is an important mediator of microbial translocation and inflammation in PWH, and that reduced gut microbiome diversity may have an important role. MDPI 2021-09-22 /pmc/articles/PMC8537977/ /pubmed/34696320 http://dx.doi.org/10.3390/v13101891 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ellis, Ronald J.
Iudicello, Jennifer E.
Heaton, Robert K.
Isnard, Stéphane
Lin, John
Routy, Jean-Pierre
Gianella, Sara
Hoenigl, Martin
Knight, Rob
Markers of Gut Barrier Function and Microbial Translocation Associate with Lower Gut Microbial Diversity in People with HIV
title Markers of Gut Barrier Function and Microbial Translocation Associate with Lower Gut Microbial Diversity in People with HIV
title_full Markers of Gut Barrier Function and Microbial Translocation Associate with Lower Gut Microbial Diversity in People with HIV
title_fullStr Markers of Gut Barrier Function and Microbial Translocation Associate with Lower Gut Microbial Diversity in People with HIV
title_full_unstemmed Markers of Gut Barrier Function and Microbial Translocation Associate with Lower Gut Microbial Diversity in People with HIV
title_short Markers of Gut Barrier Function and Microbial Translocation Associate with Lower Gut Microbial Diversity in People with HIV
title_sort markers of gut barrier function and microbial translocation associate with lower gut microbial diversity in people with hiv
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8537977/
https://www.ncbi.nlm.nih.gov/pubmed/34696320
http://dx.doi.org/10.3390/v13101891
work_keys_str_mv AT ellisronaldj markersofgutbarrierfunctionandmicrobialtranslocationassociatewithlowergutmicrobialdiversityinpeoplewithhiv
AT iudicellojennifere markersofgutbarrierfunctionandmicrobialtranslocationassociatewithlowergutmicrobialdiversityinpeoplewithhiv
AT heatonrobertk markersofgutbarrierfunctionandmicrobialtranslocationassociatewithlowergutmicrobialdiversityinpeoplewithhiv
AT isnardstephane markersofgutbarrierfunctionandmicrobialtranslocationassociatewithlowergutmicrobialdiversityinpeoplewithhiv
AT linjohn markersofgutbarrierfunctionandmicrobialtranslocationassociatewithlowergutmicrobialdiversityinpeoplewithhiv
AT routyjeanpierre markersofgutbarrierfunctionandmicrobialtranslocationassociatewithlowergutmicrobialdiversityinpeoplewithhiv
AT gianellasara markersofgutbarrierfunctionandmicrobialtranslocationassociatewithlowergutmicrobialdiversityinpeoplewithhiv
AT hoeniglmartin markersofgutbarrierfunctionandmicrobialtranslocationassociatewithlowergutmicrobialdiversityinpeoplewithhiv
AT knightrob markersofgutbarrierfunctionandmicrobialtranslocationassociatewithlowergutmicrobialdiversityinpeoplewithhiv