Gut microbiome signatures linked to HIV-1 reservoir size and viremia control
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Published:2022-04-11
Issue:1
Volume:10
Page:
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ISSN:2049-2618
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Container-title:Microbiome
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language:en
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Short-container-title:Microbiome
Author:
Borgognone AlessandraORCID, Noguera-Julian Marc, Oriol Bruna, Noël-Romas Laura, Ruiz-Riol Marta, Guillén Yolanda, Parera Mariona, Casadellà Maria, Duran Clara, Puertas Maria C., Català-Moll Francesc, De Leon Marlon, Knodel Samantha, Birse Kenzie, Manzardo Christian, Miró José M., Clotet Bonaventura, Martinez-Picado Javier, Moltó José, Mothe Beatriz, Burgener Adam, Brander Christian, Paredes Roger, Benet Susana, Brander Christian, Cedeño Samandhy, Clotet Bonaventura, Coll Pep, Llano Anuska, Martinez-Picado Javier, Marszalek Marta, Morón-López Sara, Mothe Beatriz, Paredes Roger, Puertas Maria C., Rosás-Umbert Miriam, Ruiz-Riol Marta, Escrig Roser, Gel Silvia, López Miriam, Miranda Cristina, Moltó José, Muñoz Jose, Perez-Alvarez Nuria, Puig Jordi, Revollo Boris, Toro Jessica, Barriocanal Ana María, Perez-Reche Cristina, Farré Magí, Valle Marta, Manzardo Christian, Ambrosioni Juan, Ruiz Irene, Rovira Cristina, Hurtado Carmen, Ligero Carmen, Fernández Emma, Sánchez-Palomino Sonsoles, Miró Jose M., Carrillo Antonio, Meulbroek Michael, Pujol Ferran, Saz Jorge, Borthwick Nicola, Crook Alison, Wee Edmund G., Hanke Tomáš,
Abstract
Abstract
Background
The potential role of the gut microbiome as a predictor of immune-mediated HIV-1 control in the absence of antiretroviral therapy (ART) is still unknown. In the BCN02 clinical trial, which combined the MVA.HIVconsv immunogen with the latency-reversing agent romidepsin in early-ART treated HIV-1 infected individuals, 23% (3/13) of participants showed sustained low-levels of plasma viremia during 32 weeks of a monitored ART pause (MAP). Here, we present a multi-omics analysis to identify compositional and functional gut microbiome patterns associated with HIV-1 control in the BCN02 trial.
Results
Viremic controllers during the MAP (controllers) exhibited higher Bacteroidales/Clostridiales ratio and lower microbial gene richness before vaccination and throughout the study intervention when compared to non-controllers. Longitudinal assessment indicated that the gut microbiome of controllers was enriched in pro-inflammatory bacteria and depleted in butyrate-producing bacteria and methanogenic archaea. Functional profiling also showed that metabolic pathways related to fatty acid and lipid biosynthesis were significantly increased in controllers. Fecal metaproteome analyses confirmed that baseline functional differences were mainly driven by Clostridiales. Participants with high baseline Bacteroidales/Clostridiales ratio had increased pre-existing immune activation-related transcripts. The Bacteroidales/Clostridiales ratio as well as host immune-activation signatures inversely correlated with HIV-1 reservoir size.
Conclusions
The present proof-of-concept study suggests the Bacteroidales/Clostridiales ratio as a novel gut microbiome signature associated with HIV-1 reservoir size and immune-mediated viral control after ART interruption.
Funder
instituto de salud carlos iii horizon 2020 framework programme national institutes of health canadian institutes of health research national institute for health research ministerio de ciencia, innovación y universidades institut d’investigacions biomèdiques august pi i sunyer
Publisher
Springer Science and Business Media LLC
Subject
Microbiology (medical),Microbiology
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