Gut microbiome signatures linked to HIV-1 reservoir size and viremia control

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• dc.contributor.author Borgognone, Alessandra
• dc.contributor.author Guillén, Yolanda
• dc.contributor.author BCN02 Study Group
• dc.date.accessioned 2022-10-07T06:25:43Z
• dc.date.available 2022-10-07T06:25:43Z
• dc.date.issued 2022
• dc.description.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. Video abstract.
• dc.description.sponsorship This study was funded by Instituto de Salud Carlos III through the project “PI16/01421” (co-funded by European Regional Development Fund “A way to make Europe”). The project was sponsored in part by Grifols and received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement N° 847943 (MISTRAL). The BCN02 clinical trial was an investigator-initiated study funded by the ISCIII PI15/01188 grant, the HIVACAT Catalan research program for an HIV vaccine and the Fundació Gloria Soler. Some sub-analyses of the BCN02 trial were partly funded by the European Union’s Horizon 2020 research and innovation program under grant agreement 681137-EAVI2020 and by NIH grant P01-AI131568. A.Bu lab was supported by grants from the Canadian Institutes of Health Research (HB3-164066) and the National Institutes for Health Research (R01DK112254). J.M.P lab was supported by grant PID2019-109870RB-I00 from the Spanish Ministry of Science and Innovation and in part by Grifols. J.M.M. received a personal 80:20 research grant from Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, during 2017–21.
• dc.format.mimetype application/pdf
• dc.identifier.citation Borgognone A, Noguera-Julian M, Oriol B, Noël-Romas L, Ruiz-Riol M, Guillén Y et al. Gut microbiome signatures linked to HIV-1 reservoir size and viremia control. Microbiome. 2022 Apr 11;10(1):59. DOI: 10.1186/s40168-022-01247-6
• dc.identifier.doi http://dx.doi.org/10.1186/s40168-022-01247-6
• dc.identifier.issn 2049-2618
• dc.identifier.uri http://hdl.handle.net/10230/54307
• dc.language.iso eng
• dc.publisher BioMed Central
• dc.relation.ispartof Microbiome. 2022 Apr 11;10(1):59
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/847943
• dc.rights © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Gut microbiome
• dc.subject.keyword HIV-1 post-treatment control
• dc.subject.keyword Microbiome-based predictive biomarker
• dc.subject.keyword Therapeutic HIV-1 vaccine
• dc.subject.keyword Viral reservoir size
• dc.title Gut microbiome signatures linked to HIV-1 reservoir size and viremia control
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion