Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 232-246 |
| Number of pages | 15 |
| Journal | Mucosal Immunology |
| Volume | 12 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2019 |
| Externally published | Yes |
Bibliographical note
Funding Information:We thank the members of the IGTP Genomics and Bioinformatics Core Facilities (Maria Pilar Armengol, Lauro Sumoy and Iñaki Martínez) for their contribution to this publication. This study was supported by philanthropic donations from Fundació Glòria Soler, Fundació Catalunya-La Pedrera, the Gala SIDA 2015 and 2016 editions, the Nit per la Recerca a la Catalunya Central 2015 edition, and People in Red – Barcelona 2016 edition. IrsiCaixa is supported by the RED de SIDA RD16/0025/0041 cofinanced by the ISCIII and the European Regional Development Fund (ERDF), “Investing in your future”. M.R. is funded through a FI-DGR grant (FI-B00184) from Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) at the Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya. M.L.C. is funded through the grant MTM2015-64465-C2-1-R, Spanish Ministry of Economy and Competitiveness, Spain. Funding for this research (Alexander S. Zevin and Nichole R. Klatt) was provided by the Department of Pharmaceutics at the University of Washington. The sponsors of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all study data, and had final responsibility for the decision to submit for publication.
Publisher Copyright:
© 2018, The Author(s).
