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 microbiomeremain unclear. Previous shotgunmetagenomic studies in HIV-negative subjects linked low-microbial gene counts (LGC) to gut dysbiosisin 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 nadirCD4+ T-cell counts and LGC. As in other diseases involving intestinal inflammation, the gut microbiomesof subjects with LGC were enriched in gram-negative Bacteroides, acetogenicbacteria 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 intestinalisdespite reductions in other butyrate producers. The microbiomesof 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 nadirCD4+ T-cell counts, rather than HIV-1 serostatusper se, predict the presence of gut dysbiosisin HIV-1 infected subjects. Such dysbiosisdoes not display obvious HIV-specific features; instead, it shares many similarities with other diseases featuring gut inflammation.