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 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. Fundació Glòria Soler Fundació Catalunya-La Pedrera Gala SIDA 2015-2016 Nit per la Recerca a la Catalunya Central 2015 edition People in Red-Barcelona 2016 edition RED de SIDA RD16/0025/0041 ISCIII European Regional Develpment Fund (ERDF) Agencia de Gestio d´Ajuts Universitaris i de Recerca (AGAUR) Secretaria d´Universitats i Recerca del Departament d´Economia i Coneixement de la Generalitat de Catalunya Ministerio de Economia y Competitividad. España Universidad de Whashington