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

Mucosal Immunology
Yolanda GuillénRoger Paredes

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 count...Continue Reading

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Datasets Mentioned

BETA
SRP068240

Methods Mentioned

BETA
biopsies
surgical resection
ELISA

Software Mentioned

HUMAnN
HIVACAT
ggplot2
bwa
R
metaMDS
Trimmomatic
FishTaco
Metaphlan
FishTacoPlot R package

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