Gut microbiome signatures linked to HIV-1 reservoir size and viremia control
Alessandra Borgognone, Marc Noguera-Julián, Bruna Oriol-Tordera, Laura Noël‐Romas, Marta Ruiz‐Riol, Yolanda Guillén, Mariona Parera, María Casadellà, Clara Duran, María C. Puertas, Francesc Català‐Moll, Marlon De Leon, Samantha Knodel, Kenzie Birse, Christian Manzardo, José M. Miró, Bonaventura Clotet, Javier Martínez‐Picado, José Moltó, Beatriz Mothe, Adam Burgener, Christian Brander, Roger Paredes, the BCN02 Study Group, Susana Benet, Christian Brander, Samandhy Cedeño, Bonaventura Clotet, Pep Coll, Anuska Llano, Javier Martínez‐Picado, Marta Marszalek, Sara Morón‐López, Beatriz Mothe, Roger Paredes, María C. Puertas, Míriam Rosás-Umbert, Marta Ruiz‐Riol, Roser Escrig, Sílvia Gel, Miriam Cebey‐López, Cristina Miranda, José Moltó, José F. Muñoz, Núria Pérez‐Álvarez, Jordi Puig, Boris Revollo, Jessica Toro, Ana María Barriocanal, Cristina Perez-Reche, Magı́ Farré, Marta Valle, Christian Manzardo, Juan Ambrosioni, Irene Ruíz, Cristina Rovira, Carmen Hurtado, Carmen Ligero, Emma Quiles Fernández, Sonsoles Sánchez‐Palomino, José M. Miró, Antonio Carrillo, Michael Meulbroek, Ferran Pujol, Jorge Saz, Nicola Borthwick, Alison Crook, Edmund G. Wee, Tomáš Hanke
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.