TY - JOUR
T1 - Gut dysbiosis associates with cytokine production capacity in viral-suppressed people living with HIV
AU - Zhang, Yue
AU - Andreu-Sánchez, Sergio
AU - Vadaq, Nadira
AU - Wang, Daoming
AU - Matzaraki, Vasiliki
AU - van der Heijden, Wouter A
AU - Gacesa, Ranko
AU - Weersma, Rinse K
AU - Zhernakova, Alexandra
AU - Vandekerckhove, Linos
AU - de Mast, Quirijn
AU - Joosten, Leo A B
AU - Netea, Mihai G
AU - van der Ven, André J A M
AU - Fu, Jingyuan
N1 - Copyright © 2023 Zhang, Andreu-Sánchez, Vadaq, Wang, Matzaraki, van der Heijden, Gacesa, Weersma, Zhernakova, Vandekerckhove, de Mast, Joosten, Netea, van der Ven and Fu.
PY - 2023
Y1 - 2023
N2 - BACKGROUND: People living with human immunodeficiency virus (PLHIV) are exposed to chronic immune dysregulation, even when virus replication is suppressed by antiretroviral therapy (ART). Given the emerging role of the gut microbiome in immunity, we hypothesized that the gut microbiome may be related to the cytokine production capacity of PLHIV.METHODS: To test this hypothesis, we collected metagenomic data from 143 ART-treated PLHIV and assessed the
ex vivo production capacity of eight different cytokines [interleukin-1β (IL-1β), IL-6, IL-1Ra, IL-10, IL-17, IL-22, tumor necrosis factor, and interferon-γ] in response to different stimuli. We also characterized CD4
+ T-cell counts, HIV reservoir, and other clinical parameters.
RESULTS: Compared with 190 age- and sex-matched controls and a second independent control cohort, PLHIV showed microbial dysbiosis that was correlated with viral reservoir levels (CD4
+ T-cell-associated HIV-1 DNA), cytokine production capacity, and sexual behavior. Notably, we identified two genetically different
P. copri strains that were enriched in either PLHIV or healthy controls. The control-related strain showed a stronger negative association with cytokine production capacity than the PLHIV-related strain, particularly for Pam3Cys-incuded IL-6 and IL-10 production. The control-related strain is also positively associated with CD4
+ T-cell level.
CONCLUSIONS: Our findings suggest that modulating the gut microbiome may be a strategy to modulate immune response in PLHIV.
AB - BACKGROUND: People living with human immunodeficiency virus (PLHIV) are exposed to chronic immune dysregulation, even when virus replication is suppressed by antiretroviral therapy (ART). Given the emerging role of the gut microbiome in immunity, we hypothesized that the gut microbiome may be related to the cytokine production capacity of PLHIV.METHODS: To test this hypothesis, we collected metagenomic data from 143 ART-treated PLHIV and assessed the
ex vivo production capacity of eight different cytokines [interleukin-1β (IL-1β), IL-6, IL-1Ra, IL-10, IL-17, IL-22, tumor necrosis factor, and interferon-γ] in response to different stimuli. We also characterized CD4
+ T-cell counts, HIV reservoir, and other clinical parameters.
RESULTS: Compared with 190 age- and sex-matched controls and a second independent control cohort, PLHIV showed microbial dysbiosis that was correlated with viral reservoir levels (CD4
+ T-cell-associated HIV-1 DNA), cytokine production capacity, and sexual behavior. Notably, we identified two genetically different
P. copri strains that were enriched in either PLHIV or healthy controls. The control-related strain showed a stronger negative association with cytokine production capacity than the PLHIV-related strain, particularly for Pam3Cys-incuded IL-6 and IL-10 production. The control-related strain is also positively associated with CD4
+ T-cell level.
CONCLUSIONS: Our findings suggest that modulating the gut microbiome may be a strategy to modulate immune response in PLHIV.
KW - Humans
KW - HIV
KW - Interleukin-10
KW - Interleukin-6
KW - Dysbiosis
KW - HIV Infections/drug therapy
KW - Cytokines
U2 - 10.3389/fcimb.2023.1202035
DO - 10.3389/fcimb.2023.1202035
M3 - Article
C2 - 37583444
SN - 2235-2988
VL - 13
JO - Frontiers in Cellular and Infection Microbiology
JF - Frontiers in Cellular and Infection Microbiology
M1 - 1202035
ER -