Low nadir CD4+ T-cell counts predict gut dysbiosis in HIV-1 infection

Human immunodeficiency virus (HIV)-1 infection causes severe gut and systemic immune damage, but its effects on the gut microbiome remain unclear. Previous shotgun metagenomic studies in HIV-negative subjects linked low-microbial gene counts (LGC) to gut dysbiosis in diseases featuring intestinal in...

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Autores: Guillén, Yolanda|||0000-0001-8673-6470, Noguera-Julian, Marc|||0000-0002-6194-1395, Rivera Pinto, Javier|||0000-0002-4427-6442, Casadellà, Maria|||0000-0002-4115-2305, Zevin, Alexander, Rocafort, M., Parera, M., Rodríguez, C., Arumí Rovira, Marçal, Carrillo, Jorge|||0000-0003-0221-5948, Mothe, Beatriz|||0000-0001-9975-407X, Estany Quera, Carla|||0000-0001-6993-5865, Coll, Josep, Bravo, Isabel, Herrero, Cristina, Saz, Jorge|||0000-0002-8679-634X, Sirera, Guillem|||0000-0003-4014-9355, Torrella Domingo, Adriana|||0000-0003-1848-5096, Navarro, Jordi|||0000-0002-7187-0367, Crespo Casal, Manuel|||0000-0001-9016-0515, Negredo Puigmal, Eugènia|||0000-0001-5298-1734, Brander, Christian|||0000-0002-0548-5778, Blanco, Julià|||0000-0002-2225-0217, Calle, M. Luz|||0000-0001-9334-415X, Klatt, N. R., Pérez-Álvarez, Núria|||0000-0001-6582-1553, Paredes, Roger|||0000-0002-6553-691X
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:224112
Acceso en línea:https://ddd.uab.cat/record/224112
https://dx.doi.org/urn:doi:10.1038/s41385-018-0083-7
Access Level:acceso abierto
Palabra clave:Adult
Archaea
Bacteroides
Butyrates
CD4 Lymphocyte Count
CD4-Positive T-Lymphocytes
Cross-Sectional Studies
Dysbiosis
Feces
Female
Gastrointestinal Microbiome
HIV Infections
HIV-1
Humans
Intestinal Mucosa
Male
Middle Aged
Prognosis
Descripción
Sumario:Human immunodeficiency virus (HIV)-1 infection causes severe gut and systemic immune damage, but its effects on the gut microbiome remain unclear. Previous shotgun metagenomic studies in HIV-negative subjects linked low-microbial gene counts (LGC) to gut dysbiosis in diseases featuring intestinal inflammation. Using a similar approach in 156 subjects with different HIV-1 phenotypes, we found a strong, independent, dose-effect association between nadir CD4+ T-cell counts and LGC. As in other diseases involving intestinal inflammation, the gut microbiomes of subjects with LGC were enriched in gram-negative Bacteroides, acetogenic bacteria and Proteobacteria, which are able to metabolize reactive oxygen and nitrogen species; and were depleted in oxygen-sensitive methanogenic archaea and sulfate-reducing bacteria. Interestingly, subjects with LGC also showed increased butyrate levels in direct fecal measurements, consistent with enrichment in Roseburia intestinalis despite reductions in other butyrate producers. The microbiomes of subjects with LGC were also enriched in bacterial virulence factors, as well as in genes associated with beta-lactam, lincosamide, tetracycline, and macrolide resistance. Thus, low nadir CD4+ T-cell counts, rather than HIV-1 serostatus per se, predict the presence of gut dysbiosis in HIV-1 infected subjects. Such dysbiosis does not display obvious HIV-specific features; instead, it shares many similarities with other diseases featuring gut inflammation.

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